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2. Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)

Author

Cossarizza, A, Chang, H, Radbruch, A, Abrignani, S, Addo, R, Akdis, M, Andra, I, Andreata, F, Annunziato, F, Arranz, E, Bacher, P, Bari, S, Barnaba, V, Barros-Martins, J, Baumjohann, D, Beccaria, C, Bernardo, D, Boardman, D, Borger, J, Bottcher, C, Brockmann, L, Burns, M, Busch, D, Cameron, G, Cammarata, I, Cassotta, A, Chang, Y, Chirdo, F, Christakou, E, Cicin-Sain, L, Cook, L, Corbett, A, Cornelis, R, Cosmi, L, Davey, M, De Biasi, S, De Simone, G, del Zotto, G, Delacher, M, Di Rosa, F, Santo, J, Diefenbach, A, Dong, J, Dorner, T, Dress, R, Dutertre, C, Eckle, S, Eede, P, Evrard, M, Falk, C, Feuerer, M, Fillatreau, S, Fiz-Lopez, A, Follo, M, Foulds, G, Frobel, J, Gagliani, N, Galletti, G, Gangaev, A, Garbi, N, Garrote, J, Geginat, J, Gherardin, N, Gibellini, L, Ginhoux, F, Godfrey, D, Gruarin, P, Haftmann, C, Hansmann, L, Harpur, C, Hayday, A, Heine, G, Hernandez, D, Herrmann, M, Hoelsken, O, Huang, Q, Huber, S, Huber, J, Huehn, J, Hundemer, M, Hwang, W, Iannacone, M, Ivison, S, Jack, H, Jani, P, Keller, B, Kessler, N, Ketelaars, S, Knop, L, Knopf, J, Koay, H, Kobow, K, Kriegsmann, K, Kristyanto, H, Krueger, A, Kuehne, J, Kunze-Schumacher, H, Kvistborg, P, Kwok, I, Latorre, D, Lenz, D, Levings, M, Lino, A, Liotta, F, Long, H, Lugli, E, Macdonald, K, Maggi, L, Maini, M, Mair, F, Manta, C, Manz, R, Mashreghi, M, Mazzoni, A, Mccluskey, J, Mei, H, Melchers, F, Melzer, S, Mielenz, D, Monin, L, Moretta, L, Multhoff, G, Munoz, L, Munoz-Ruiz, M, Muscate, F, Natalini, A, Neumann, K, Ng, L, Niedobitek, A, Niemz, J, Almeida, L, Notarbartolo, S, Ostendorf, L, Pallett, L, Patel, A, Percin, G, Peruzzi, G, Pinti, M, Pockley, A, Pracht, K, Prinz, I, Pujol-Autonell, I, Pulvirenti, N, Quatrini, L, Quinn, K, Radbruch, H, Rhys, H, Rodrigo, M, Romagnani, C, Saggau, C, Sakaguchi, S, Sallusto, F, Sanderink, L, Sandrock, I, Schauer, C, Scheffold, A, Scherer, H, Schiemann, M, Schildberg, F, Schober, K, Schoen, J, Schuh, W, Schuler, T, Schulz, A, Schulz, S, Schulze, J, Simonetti, S, Singh, J, Sitnik, K, Stark, R, Starossom, S, Stehle, C, Szelinski, F, Tan, L, Tarnok, A, Tornack, J, Tree, T, van Beek, J, van de Veen, W, van Gisbergen, K, Vasco, C, Verheyden, N, von Borstel, A, Ward-Hartstonge, K, Warnatz, K, Waskow, C, Wiedemann, A, Wilharm, A, Wing, J, Wirz, O, Wittner, J, Yang, J, Cossarizza A., Chang H. -D., Radbruch A., Abrignani S., Addo R., Akdis M., Andra I., Andreata F., Annunziato F., Arranz E., Bacher P., Bari S., Barnaba V., Barros-Martins J., Baumjohann D., Beccaria C. G., Bernardo D., Boardman D. A., Borger J., Bottcher C., Brockmann L., Burns M., Busch D. H., Cameron G., Cammarata I., Cassotta A., Chang Y., Chirdo F. G., Christakou E., Cicin-Sain L., Cook L., Corbett A. J., Cornelis R., Cosmi L., Davey M. S., De Biasi S., De Simone G., del Zotto G., Delacher M., Di Rosa F., Santo J. D., Diefenbach A., Dong J., Dorner T., Dress R. J., Dutertre C. -A., Eckle S. B. G., Eede P., Evrard M., Falk C. S., Feuerer M., Fillatreau S., Fiz-Lopez A., Follo M., Foulds G. A., Frobel J., Gagliani N., Galletti G., Gangaev A., Garbi N., Garrote J. A., Geginat J., Gherardin N. A., Gibellini L., Ginhoux F., Godfrey D. I., Gruarin P., Haftmann C., Hansmann L., Harpur C. M., Hayday A. C., Heine G., Hernandez D. C., Herrmann M., Hoelsken O., Huang Q., Huber S., Huber J. E., Huehn J., Hundemer M., Hwang W. Y. K., Iannacone M., Ivison S. M., Jack H. -M., Jani P. K., Keller B., Kessler N., Ketelaars S., Knop L., Knopf J., Koay H. -F., Kobow K., Kriegsmann K., Kristyanto H., Krueger A., Kuehne J. F., Kunze-Schumacher H., Kvistborg P., Kwok I., Latorre D., Lenz D., Levings M. K., Lino A. C., Liotta F., Long H. M., Lugli E., MacDonald K. N., Maggi L., Maini M. K., Mair F., Manta C., Manz R. A., Mashreghi M. -F., Mazzoni A., McCluskey J., Mei H. E., Melchers F., Melzer S., Mielenz D., Monin L., Moretta L., Multhoff G., Munoz L. E., Munoz-Ruiz M., Muscate F., Natalini A., Neumann K., Ng L. G., Niedobitek A., Niemz J., Almeida L. N., Notarbartolo S., Ostendorf L., Pallett L. J., Patel A. A., Percin G. I., Peruzzi G., Pinti M., Pockley A. G., Pracht K., Prinz I., Pujol-Autonell I., Pulvirenti N., Quatrini L., Quinn K. M., Radbruch H., Rhys H., Rodrigo M. B., Romagnani C., Saggau C., Sakaguchi S., Sallusto F., Sanderink L., Sandrock I., Schauer C., Scheffold A., Scherer H. U., Schiemann M., Schildberg F. A., Schober K., Schoen J., Schuh W., Schuler T., Schulz A. R., Schulz S., Schulze J., Simonetti S., Singh J., Sitnik K. M., Stark R., Starossom S., Stehle C., Szelinski F., Tan L., Tarnok A., Tornack J., Tree T. I. M., van Beek J. J. P., van de Veen W., van Gisbergen K., Vasco C., Verheyden N. A., von Borstel A., Ward-Hartstonge K. A., Warnatz K., Waskow C., Wiedemann A., Wilharm A., Wing J., Wirz O., Wittner J., Yang J. H. M., Yang J., Cossarizza, A, Chang, H, Radbruch, A, Abrignani, S, Addo, R, Akdis, M, Andra, I, Andreata, F, Annunziato, F, Arranz, E, Bacher, P, Bari, S, Barnaba, V, Barros-Martins, J, Baumjohann, D, Beccaria, C, Bernardo, D, Boardman, D, Borger, J, Bottcher, C, Brockmann, L, Burns, M, Busch, D, Cameron, G, Cammarata, I, Cassotta, A, Chang, Y, Chirdo, F, Christakou, E, Cicin-Sain, L, Cook, L, Corbett, A, Cornelis, R, Cosmi, L, Davey, M, De Biasi, S, De Simone, G, del Zotto, G, Delacher, M, Di Rosa, F, Santo, J, Diefenbach, A, Dong, J, Dorner, T, Dress, R, Dutertre, C, Eckle, S, Eede, P, Evrard, M, Falk, C, Feuerer, M, Fillatreau, S, Fiz-Lopez, A, Follo, M, Foulds, G, Frobel, J, Gagliani, N, Galletti, G, Gangaev, A, Garbi, N, Garrote, J, Geginat, J, Gherardin, N, Gibellini, L, Ginhoux, F, Godfrey, D, Gruarin, P, Haftmann, C, Hansmann, L, Harpur, C, Hayday, A, Heine, G, Hernandez, D, Herrmann, M, Hoelsken, O, Huang, Q, Huber, S, Huber, J, Huehn, J, Hundemer, M, Hwang, W, Iannacone, M, Ivison, S, Jack, H, Jani, P, Keller, B, Kessler, N, Ketelaars, S, Knop, L, Knopf, J, Koay, H, Kobow, K, Kriegsmann, K, Kristyanto, H, Krueger, A, Kuehne, J, Kunze-Schumacher, H, Kvistborg, P, Kwok, I, Latorre, D, Lenz, D, Levings, M, Lino, A, Liotta, F, Long, H, Lugli, E, Macdonald, K, Maggi, L, Maini, M, Mair, F, Manta, C, Manz, R, Mashreghi, M, Mazzoni, A, Mccluskey, J, Mei, H, Melchers, F, Melzer, S, Mielenz, D, Monin, L, Moretta, L, Multhoff, G, Munoz, L, Munoz-Ruiz, M, Muscate, F, Natalini, A, Neumann, K, Ng, L, Niedobitek, A, Niemz, J, Almeida, L, Notarbartolo, S, Ostendorf, L, Pallett, L, Patel, A, Percin, G, Peruzzi, G, Pinti, M, Pockley, A, Pracht, K, Prinz, I, Pujol-Autonell, I, Pulvirenti, N, Quatrini, L, Quinn, K, Radbruch, H, Rhys, H, Rodrigo, M, Romagnani, C, Saggau, C, Sakaguchi, S, Sallusto, F, Sanderink, L, Sandrock, I, Schauer, C, Scheffold, A, Scherer, H, Schiemann, M, Schildberg, F, Schober, K, Schoen, J, Schuh, W, Schuler, T, Schulz, A, Schulz, S, Schulze, J, Simonetti, S, Singh, J, Sitnik, K, Stark, R, Starossom, S, Stehle, C, Szelinski, F, Tan, L, Tarnok, A, Tornack, J, Tree, T, van Beek, J, van de Veen, W, van Gisbergen, K, Vasco, C, Verheyden, N, von Borstel, A, Ward-Hartstonge, K, Warnatz, K, Waskow, C, Wiedemann, A, Wilharm, A, Wing, J, Wirz, O, Wittner, J, Yang, J, Cossarizza A., Chang H. -D., Radbruch A., Abrignani S., Addo R., Akdis M., Andra I., Andreata F., Annunziato F., Arranz E., Bacher P., Bari S., Barnaba V., Barros-Martins J., Baumjohann D., Beccaria C. G., Bernardo D., Boardman D. A., Borger J., Bottcher C., Brockmann L., Burns M., Busch D. H., Cameron G., Cammarata I., Cassotta A., Chang Y., Chirdo F. G., Christakou E., Cicin-Sain L., Cook L., Corbett A. J., Cornelis R., Cosmi L., Davey M. S., De Biasi S., De Simone G., del Zotto G., Delacher M., Di Rosa F., Santo J. D., Diefenbach A., Dong J., Dorner T., Dress R. J., Dutertre C. -A., Eckle S. B. G., Eede P., Evrard M., Falk C. S., Feuerer M., Fillatreau S., Fiz-Lopez A., Follo M., Foulds G. A., Frobel J., Gagliani N., Galletti G., Gangaev A., Garbi N., Garrote J. A., Geginat J., Gherardin N. A., Gibellini L., Ginhoux F., Godfrey D. I., Gruarin P., Haftmann C., Hansmann L., Harpur C. M., Hayday A. C., Heine G., Hernandez D. C., Herrmann M., Hoelsken O., Huang Q., Huber S., Huber J. E., Huehn J., Hundemer M., Hwang W. Y. K., Iannacone M., Ivison S. M., Jack H. -M., Jani P. K., Keller B., Kessler N., Ketelaars S., Knop L., Knopf J., Koay H. -F., Kobow K., Kriegsmann K., Kristyanto H., Krueger A., Kuehne J. F., Kunze-Schumacher H., Kvistborg P., Kwok I., Latorre D., Lenz D., Levings M. K., Lino A. C., Liotta F., Long H. M., Lugli E., MacDonald K. N., Maggi L., Maini M. K., Mair F., Manta C., Manz R. A., Mashreghi M. -F., Mazzoni A., McCluskey J., Mei H. E., Melchers F., Melzer S., Mielenz D., Monin L., Moretta L., Multhoff G., Munoz L. E., Munoz-Ruiz M., Muscate F., Natalini A., Neumann K., Ng L. G., Niedobitek A., Niemz J., Almeida L. N., Notarbartolo S., Ostendorf L., Pallett L. J., Patel A. A., Percin G. I., Peruzzi G., Pinti M., Pockley A. G., Pracht K., Prinz I., Pujol-Autonell I., Pulvirenti N., Quatrini L., Quinn K. M., Radbruch H., Rhys H., Rodrigo M. B., Romagnani C., Saggau C., Sakaguchi S., Sallusto F., Sanderink L., Sandrock I., Schauer C., Scheffold A., Scherer H. U., Schiemann M., Schildberg F. A., Schober K., Schoen J., Schuh W., Schuler T., Schulz A. R., Schulz S., Schulze J., Simonetti S., Singh J., Sitnik K. M., Stark R., Starossom S., Stehle C., Szelinski F., Tan L., Tarnok A., Tornack J., Tree T. I. M., van Beek J. J. P., van de Veen W., van Gisbergen K., Vasco C., Verheyden N. A., von Borstel A., Ward-Hartstonge K. A., Warnatz K., Waskow C., Wiedemann A., Wilharm A., Wing J., Wirz O., Wittner J., Yang J. H. M., and Yang J.

Abstract

The third edition of Flow Cytometry Guidelines provides the key aspects to consider when performing flow cytometry experiments and includes comprehensive sections describing phenotypes and functional assays of all major human and murine immune cell subsets. Notably, the Guidelines contain helpful tables highlighting phenotypes and key differences between human and murine cells. Another useful feature of this edition is the flow cytometry analysis of clinical samples with examples of flow cytometry applications in the context of autoimmune diseases, cancers as well as acute and chronic infectious diseases. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid. All sections are written and peer-reviewed by leading flow cytometry experts and immunologists, making this edition an essential and state-of-the-art handbook for basic and clinical researchers.

Published
2021

3. Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)

Author

Cossarizza, A, Chang, H-D, Radbruch, A, Acs, A, Adam, D, Adam-Klages, S, Agace, WW, Aghaeepour, N, Akdis, M, Allez, M, Almeida, LN, Alvisi, G, Anderson, G, Andrae, I, Annunziato, F, Anselmo, A, Bacher, P, Baldari, CT, Bari, S, Barnaba, V, Barros-Martins, J, Battistini, L, Bauer, W, Baumgart, S, Baumgarth, N, Baumjohann, D, Baying, B, Bebawy, M, Becher, B, Beisker, W, Benes, V, Beyaert, R, Blanco, A, Boardman, DA, Bogdan, C, Borger, JG, Borsellino, G, Boulais, PE, Bradford, JA, Brenner, D, Brinkman, RR, Brooks, AES, Busch, DH, Buescher, M, Bushnell, TP, Calzetti, F, Cameron, G, Cammarata, I, Cao, X, Cardell, SL, Casola, S, Cassatella, MA, Cavani, A, Celada, A, Chatenoud, L, Chattopadhyay, PK, Chow, S, Christakou, E, Cicin-Sain, L, Clerici, M, Colombo, FS, Cook, L, Cooke, A, Cooper, AM, Corbett, AJ, Cosma, A, Cosmi, L, Coulie, PG, Cumano, A, Cvetkovic, L, Dang, VD, Dang-Heine, C, Davey, MS, Davies, D, De Biasi, S, Del Zotto, G, Dela Cruz, GV, Delacher, M, Della Bella, S, Dellabona, P, Deniz, G, Dessing, M, Di Santo, JP, Diefenbach, A, Dieli, F, Dolf, A, Doerner, T, Dress, RJ, Dudziak, D, Dustin, M, Dutertre, C-A, Ebner, F, Eckle, SBG, Edinger, M, Eede, P, Ehrhardt, GRA, Eich, M, Engel, P, Engelhardt, B, Erdei, A, Esser, C, Everts, B, Evrard, M, Falk, CS, Fehniger, TA, Felipo-Benavent, M, Ferry, H, Feuerer, M, Filby, A, Filkor, K, Fillatreau, S, Follo, M, Foerster, I, Foster, J, Foulds, GA, Frehse, B, Frenette, PS, Frischbutter, S, Fritzsche, W, Galbraith, DW, Gangaev, A, Garbi, N, Gaudilliere, B, Gazzinelli, RT, Geginat, J, Gerner, W, Gherardin, NA, Ghoreschi, K, Gibellini, L, Ginhoux, F, Goda, K, Godfrey, DI, Goettlinger, C, Gonzalez-Navajas, JM, Goodyear, CS, Gori, A, Grogan, JL, Grummitt, D, Gruetzkau, A, Haftmann, C, Hahn, J, Hammad, H, Haemmerling, G, Hansmann, L, Hansson, G, Harpur, CM, Hartmann, S, Hauser, A, Hauser, AE, Haviland, DL, Hedley, D, Hernandez, DC, Herrera, G, Herrmann, M, Hess, C, Hoefer, T, Hoffmann, P, Hogquist, K, Holland, T, Hollt, T, Holmdahl, R, Hombrink, P, Houston, JP, Hoyer, BF, Huang, B, Huang, F-P, Huber, JE, Huehn, J, Hundemer, M, Hunter, CA, Hwang, WYK, Iannone, A, Ingelfinger, F, Ivison, SM, Jaeck, H-M, Jani, PK, Javega, B, Jonjic, S, Kaiser, T, Kalina, T, Kamradt, T, Kaufmann, SHE, Keller, B, Ketelaars, SLC, Khalilnezhad, A, Khan, S, Kisielow, J, Klenerman, P, Knopf, J, Koay, H-F, Kobow, K, Kolls, JK, Kong, WT, Kopf, M, Korn, T, Kriegsmann, K, Kristyanto, H, Kroneis, T, Krueger, A, Kuehne, J, Kukat, C, Kunkel, D, Kunze-Schumacher, H, Kurosaki, T, Kurts, C, Kvistborg, P, Kwok, I, Landry, J, Lantz, O, Lanuti, P, LaRosa, F, Lehuen, A, LeibundGut-Landmann, S, Leipold, MD, Leung, LYT, Levings, MK, Lino, AC, Liotta, F, Litwin, V, Liu, Y, Ljunggren, H-G, Lohoff, M, Lombardi, G, Lopez, L, Lopez-Botet, M, Lovett-Racke, AE, Lubberts, E, Luche, H, Ludewig, B, Lugli, E, Lunemann, S, Maecker, HT, Maggi, L, Maguire, O, Mair, F, Mair, KH, Mantovani, A, Manz, RA, Marshall, AJ, Martinez-Romero, A, Martrus, G, Marventano, I, Maslinski, W, Matarese, G, Mattioli, AV, Maueroder, C, Mazzoni, A, McCluskey, J, McGrath, M, McGuire, HM, McInnes, IB, Mei, HE, Melchers, F, Melzer, S, Mielenz, D, Miller, SD, Mills, KHG, Minderman, H, Mjosberg, J, Moore, J, Moran, B, Moretta, L, Mosmann, TR, Mueller, S, Multhoff, G, Munoz, LE, Munz, C, Nakayama, T, Nasi, M, Neumann, K, Ng, LG, Niedobitek, A, Nourshargh, S, Nunez, G, O'Connor, J-E, Ochel, A, Oja, A, Ordonez, D, Orfao, A, Orlowski-Oliver, E, Ouyang, W, Oxenius, A, Palankar, R, Panse, I, Pattanapanyasat, K, Paulsen, M, Pavlinic, D, Penter, L, Peterson, P, Peth, C, Petriz, J, Piancone, F, Pickl, WF, Piconese, S, Pinti, M, Pockley, AG, Podolska, MJ, Poon, Z, Pracht, K, Prinz, I, Pucillo, CEM, Quataert, SA, Quatrini, L, Quinn, KM, Radbruch, H, Radstake, TRDJ, Rahmig, S, Rahn, H-P, Rajwa, B, Ravichandran, G, Raz, Y, Rebhahn, JA, Recktenwald, D, Reimer, D, Reis e Sousa, C, Remmerswaal, EBM, Richter, L, Rico, LG, Riddell, A, Rieger, AM, Robinson, JP, Romagnani, C, Rubartelli, A, Ruland, J, Saalmueller, A, Saeys, Y, Saito, T, Sakaguchi, S, Sala-de-Oyanguren, F, Samstag, Y, Sanderson, S, Sandrock, I, Santoni, A, Sanz, RB, Saresella, M, Sautes-Fridman, C, Sawitzki, B, Schadt, L, Scheffold, A, Scherer, HU, Schiemann, M, Schildberg, FA, Schimisky, E, Schlitzer, A, Schlosser, J, Schmid, S, Schmitt, S, Schober, K, Schraivogel, D, Schuh, W, Schueler, T, Schulte, R, Schulz, AR, Schulz, SR, Scotta, C, Scott-Algara, D, Sester, DP, Shankey, TV, Silva-Santos, B, Simon, AK, Sitnik, KM, Sozzani, S, Speiser, DE, Spidlen, J, Stahlberg, A, Stall, AM, Stanley, N, Stark, R, Stehle, C, Steinmetz, T, Stockinger, H, Takahama, Y, Takeda, K, Tan, L, Tarnok, A, Tiegs, G, Toldi, G, Tornack, J, Traggiai, E, Trebak, M, Tree, TIM, Trotter, J, Trowsdale, J, Tsoumakidou, M, Ulrich, H, Urbanczyk, S, van de Veen, W, van den Broek, M, van der Pol, E, Van Gassen, S, Van Isterdael, G, van Lier, RAW, Veldhoen, M, Vento-Asturias, S, Vieira, P, Voehringer, D, Volk, H-D, von Borstel, A, von Volkmann, K, Waisman, A, Walker, RV, Wallace, PK, Wang, SA, Wang, XM, Ward, MD, Ward-Hartstonge, KA, Warnatz, K, Warnes, G, Warth, S, Waskow, C, Watson, JV, Watzl, C, Wegener, L, Weisenburger, T, Wiedemann, A, Wienands, J, Wilharm, A, Wilkinson, RJ, Willimsky, G, Wing, JB, Winkelmann, R, Winkler, TH, Wirz, OF, Wong, A, Wurst, P, Yang, JHM, Yang, J, Yazdanbakhsh, M, Yu, L, Yue, A, Zhang, H, Zhao, Y, Ziegler, SM, Zielinski, C, Zimmermann, J, Zychlinsky, A, Cossarizza, A, Chang, H-D, Radbruch, A, Acs, A, Adam, D, Adam-Klages, S, Agace, WW, Aghaeepour, N, Akdis, M, Allez, M, Almeida, LN, Alvisi, G, Anderson, G, Andrae, I, Annunziato, F, Anselmo, A, Bacher, P, Baldari, CT, Bari, S, Barnaba, V, Barros-Martins, J, Battistini, L, Bauer, W, Baumgart, S, Baumgarth, N, Baumjohann, D, Baying, B, Bebawy, M, Becher, B, Beisker, W, Benes, V, Beyaert, R, Blanco, A, Boardman, DA, Bogdan, C, Borger, JG, Borsellino, G, Boulais, PE, Bradford, JA, Brenner, D, Brinkman, RR, Brooks, AES, Busch, DH, Buescher, M, Bushnell, TP, Calzetti, F, Cameron, G, Cammarata, I, Cao, X, Cardell, SL, Casola, S, Cassatella, MA, Cavani, A, Celada, A, Chatenoud, L, Chattopadhyay, PK, Chow, S, Christakou, E, Cicin-Sain, L, Clerici, M, Colombo, FS, Cook, L, Cooke, A, Cooper, AM, Corbett, AJ, Cosma, A, Cosmi, L, Coulie, PG, Cumano, A, Cvetkovic, L, Dang, VD, Dang-Heine, C, Davey, MS, Davies, D, De Biasi, S, Del Zotto, G, Dela Cruz, GV, Delacher, M, Della Bella, S, Dellabona, P, Deniz, G, Dessing, M, Di Santo, JP, Diefenbach, A, Dieli, F, Dolf, A, Doerner, T, Dress, RJ, Dudziak, D, Dustin, M, Dutertre, C-A, Ebner, F, Eckle, SBG, Edinger, M, Eede, P, Ehrhardt, GRA, Eich, M, Engel, P, Engelhardt, B, Erdei, A, Esser, C, Everts, B, Evrard, M, Falk, CS, Fehniger, TA, Felipo-Benavent, M, Ferry, H, Feuerer, M, Filby, A, Filkor, K, Fillatreau, S, Follo, M, Foerster, I, Foster, J, Foulds, GA, Frehse, B, Frenette, PS, Frischbutter, S, Fritzsche, W, Galbraith, DW, Gangaev, A, Garbi, N, Gaudilliere, B, Gazzinelli, RT, Geginat, J, Gerner, W, Gherardin, NA, Ghoreschi, K, Gibellini, L, Ginhoux, F, Goda, K, Godfrey, DI, Goettlinger, C, Gonzalez-Navajas, JM, Goodyear, CS, Gori, A, Grogan, JL, Grummitt, D, Gruetzkau, A, Haftmann, C, Hahn, J, Hammad, H, Haemmerling, G, Hansmann, L, Hansson, G, Harpur, CM, Hartmann, S, Hauser, A, Hauser, AE, Haviland, DL, Hedley, D, Hernandez, DC, Herrera, G, Herrmann, M, Hess, C, Hoefer, T, Hoffmann, P, Hogquist, K, Holland, T, Hollt, T, Holmdahl, R, Hombrink, P, Houston, JP, Hoyer, BF, Huang, B, Huang, F-P, Huber, JE, Huehn, J, Hundemer, M, Hunter, CA, Hwang, WYK, Iannone, A, Ingelfinger, F, Ivison, SM, Jaeck, H-M, Jani, PK, Javega, B, Jonjic, S, Kaiser, T, Kalina, T, Kamradt, T, Kaufmann, SHE, Keller, B, Ketelaars, SLC, Khalilnezhad, A, Khan, S, Kisielow, J, Klenerman, P, Knopf, J, Koay, H-F, Kobow, K, Kolls, JK, Kong, WT, Kopf, M, Korn, T, Kriegsmann, K, Kristyanto, H, Kroneis, T, Krueger, A, Kuehne, J, Kukat, C, Kunkel, D, Kunze-Schumacher, H, Kurosaki, T, Kurts, C, Kvistborg, P, Kwok, I, Landry, J, Lantz, O, Lanuti, P, LaRosa, F, Lehuen, A, LeibundGut-Landmann, S, Leipold, MD, Leung, LYT, Levings, MK, Lino, AC, Liotta, F, Litwin, V, Liu, Y, Ljunggren, H-G, Lohoff, M, Lombardi, G, Lopez, L, Lopez-Botet, M, Lovett-Racke, AE, Lubberts, E, Luche, H, Ludewig, B, Lugli, E, Lunemann, S, Maecker, HT, Maggi, L, Maguire, O, Mair, F, Mair, KH, Mantovani, A, Manz, RA, Marshall, AJ, Martinez-Romero, A, Martrus, G, Marventano, I, Maslinski, W, Matarese, G, Mattioli, AV, Maueroder, C, Mazzoni, A, McCluskey, J, McGrath, M, McGuire, HM, McInnes, IB, Mei, HE, Melchers, F, Melzer, S, Mielenz, D, Miller, SD, Mills, KHG, Minderman, H, Mjosberg, J, Moore, J, Moran, B, Moretta, L, Mosmann, TR, Mueller, S, Multhoff, G, Munoz, LE, Munz, C, Nakayama, T, Nasi, M, Neumann, K, Ng, LG, Niedobitek, A, Nourshargh, S, Nunez, G, O'Connor, J-E, Ochel, A, Oja, A, Ordonez, D, Orfao, A, Orlowski-Oliver, E, Ouyang, W, Oxenius, A, Palankar, R, Panse, I, Pattanapanyasat, K, Paulsen, M, Pavlinic, D, Penter, L, Peterson, P, Peth, C, Petriz, J, Piancone, F, Pickl, WF, Piconese, S, Pinti, M, Pockley, AG, Podolska, MJ, Poon, Z, Pracht, K, Prinz, I, Pucillo, CEM, Quataert, SA, Quatrini, L, Quinn, KM, Radbruch, H, Radstake, TRDJ, Rahmig, S, Rahn, H-P, Rajwa, B, Ravichandran, G, Raz, Y, Rebhahn, JA, Recktenwald, D, Reimer, D, Reis e Sousa, C, Remmerswaal, EBM, Richter, L, Rico, LG, Riddell, A, Rieger, AM, Robinson, JP, Romagnani, C, Rubartelli, A, Ruland, J, Saalmueller, A, Saeys, Y, Saito, T, Sakaguchi, S, Sala-de-Oyanguren, F, Samstag, Y, Sanderson, S, Sandrock, I, Santoni, A, Sanz, RB, Saresella, M, Sautes-Fridman, C, Sawitzki, B, Schadt, L, Scheffold, A, Scherer, HU, Schiemann, M, Schildberg, FA, Schimisky, E, Schlitzer, A, Schlosser, J, Schmid, S, Schmitt, S, Schober, K, Schraivogel, D, Schuh, W, Schueler, T, Schulte, R, Schulz, AR, Schulz, SR, Scotta, C, Scott-Algara, D, Sester, DP, Shankey, TV, Silva-Santos, B, Simon, AK, Sitnik, KM, Sozzani, S, Speiser, DE, Spidlen, J, Stahlberg, A, Stall, AM, Stanley, N, Stark, R, Stehle, C, Steinmetz, T, Stockinger, H, Takahama, Y, Takeda, K, Tan, L, Tarnok, A, Tiegs, G, Toldi, G, Tornack, J, Traggiai, E, Trebak, M, Tree, TIM, Trotter, J, Trowsdale, J, Tsoumakidou, M, Ulrich, H, Urbanczyk, S, van de Veen, W, van den Broek, M, van der Pol, E, Van Gassen, S, Van Isterdael, G, van Lier, RAW, Veldhoen, M, Vento-Asturias, S, Vieira, P, Voehringer, D, Volk, H-D, von Borstel, A, von Volkmann, K, Waisman, A, Walker, RV, Wallace, PK, Wang, SA, Wang, XM, Ward, MD, Ward-Hartstonge, KA, Warnatz, K, Warnes, G, Warth, S, Waskow, C, Watson, JV, Watzl, C, Wegener, L, Weisenburger, T, Wiedemann, A, Wienands, J, Wilharm, A, Wilkinson, RJ, Willimsky, G, Wing, JB, Winkelmann, R, Winkler, TH, Wirz, OF, Wong, A, Wurst, P, Yang, JHM, Yang, J, Yazdanbakhsh, M, Yu, L, Yue, A, Zhang, H, Zhao, Y, Ziegler, SM, Zielinski, C, Zimmermann, J, and Zychlinsky, A

Abstract

These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.

Published
2019

4. Functionalized conducting polymers with polyazulene backbone

Author

Daub, Joerg, Feuerer, M., Mirlach, A., and Salbeck, Josef

Subjects
540 Chemie, ddc:540, ddc:530, 530 Physik
Abstract

Redox-active anthraquinone and ferrocene functional groups covalently linked to electronically conducting polyazulenes (PA) are accessible by electropolymerization of the C-2 substituted azulenes 1 and 2. The polymer films were characterized by electrochemical and spectroelectrochemical methods.

Published
1991

10. Identification of nonlymphoid-tissue regulatory T cell precursors

Author

Delacher, M., Imbusch, C., Hotz-Wagenblatt, A., Mallm, J. -P, Bauer, K., Riegel, D., Rendeiro, A., Bittner, S., Sanderink, L., Pant, A., Braband, K., Echtenachter, B., Hoffmann, P., Edinger, M., Bock, C., Rehli, M., Benedikt Brors, Schmidl, C., and Feuerer, M.

12. Enrichment of functional CD8 memory T cells specific for MUC1 in Bone Marrow of Multiple Myeloma Patients.

Author

Witzens, M., Choi, C., Bucur, M., Feuerer, M., Sommerfeldt, N., Trojan, A., Ho, A., Schirrmacher, V., Goldschmidt, H., and Beckhove, P.

Subjects
BONE marrow, MULTIPLE myeloma, T cells, CANCER cells, IMMUNE response, LYMPHOCYTES
Abstract

The article investigates the content and reactivity of MUC-1 specific memory T cells in bone marrow (BM) compared to PB from multiple myeloma (MM) patients with respect to possible use in immunotherapeutic strategies. It shows that MUC1 specific T cells are highly enriched in PB and BM of about 50 percent of MM patients indicating induction and maintainance of tumor cell directed immune responses during the course of disease.

Published
2004
Full Text
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13. Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)

Author

Andrea Cossarizza, Hyun‐Dong Chang, Andreas Radbruch, Sergio Abrignani, Richard Addo, Mübeccel Akdis, Immanuel Andrä, Francesco Andreata, Francesco Annunziato, Eduardo Arranz, Petra Bacher, Sudipto Bari, Vincenzo Barnaba, Joana Barros‐Martins, Dirk Baumjohann, Cristian G. Beccaria, David Bernardo, Dominic A. Boardman, Jessica Borger, Chotima Böttcher, Leonie Brockmann, Marie Burns, Dirk H. Busch, Garth Cameron, Ilenia Cammarata, Antonino Cassotta, Yinshui Chang, Fernando Gabriel Chirdo, Eleni Christakou, Luka Čičin‐Šain, Laura Cook, Alexandra J. Corbett, Rebecca Cornelis, Lorenzo Cosmi, Martin S. Davey, Sara De Biasi, Gabriele De Simone, Genny del Zotto, Michael Delacher, Francesca Di Rosa, James Di Santo, Andreas Diefenbach, Jun Dong, Thomas Dörner, Regine J. Dress, Charles‐Antoine Dutertre, Sidonia B. G. Eckle, Pascale Eede, Maximilien Evrard, Christine S. Falk, Markus Feuerer, Simon Fillatreau, Aida Fiz‐Lopez, Marie Follo, Gemma A. Foulds, Julia Fröbel, Nicola Gagliani, Giovanni Galletti, Anastasia Gangaev, Natalio Garbi, José Antonio Garrote, Jens Geginat, Nicholas A. Gherardin, Lara Gibellini, Florent Ginhoux, Dale I. Godfrey, Paola Gruarin, Claudia Haftmann, Leo Hansmann, Christopher M. Harpur, Adrian C. Hayday, Guido Heine, Daniela Carolina Hernández, Martin Herrmann, Oliver Hoelsken, Qing Huang, Samuel Huber, Johanna E. Huber, Jochen Huehn, Michael Hundemer, William Y. K. Hwang, Matteo Iannacone, Sabine M. Ivison, Hans‐Martin Jäck, Peter K. Jani, Baerbel Keller, Nina Kessler, Steven Ketelaars, Laura Knop, Jasmin Knopf, Hui‐Fern Koay, Katja Kobow, Katharina Kriegsmann, H. Kristyanto, Andreas Krueger, Jenny F. Kuehne, Heike Kunze‐Schumacher, Pia Kvistborg, Immanuel Kwok, Daniela Latorre, Daniel Lenz, Megan K. Levings, Andreia C. Lino, Francesco Liotta, Heather M. Long, Enrico Lugli, Katherine N. MacDonald, Laura Maggi, Mala K. Maini, Florian Mair, Calin Manta, Rudolf Armin Manz, Mir‐Farzin Mashreghi, Alessio Mazzoni, James McCluskey, Henrik E. Mei, Fritz Melchers, Susanne Melzer, Dirk Mielenz, Leticia Monin, Lorenzo Moretta, Gabriele Multhoff, Luis Enrique Muñoz, Miguel Muñoz‐Ruiz, Franziska Muscate, Ambra Natalini, Katrin Neumann, Lai Guan Ng, Antonia Niedobitek, Jana Niemz, Larissa Nogueira Almeida, Samuele Notarbartolo, Lennard Ostendorf, Laura J. Pallett, Amit A. Patel, Gulce Itir Percin, Giovanna Peruzzi, Marcello Pinti, A. Graham Pockley, Katharina Pracht, Immo Prinz, Irma Pujol‐Autonell, Nadia Pulvirenti, Linda Quatrini, Kylie M. Quinn, Helena Radbruch, Hefin Rhys, Maria B. Rodrigo, Chiara Romagnani, Carina Saggau, Shimon Sakaguchi, Federica Sallusto, Lieke Sanderink, Inga Sandrock, Christine Schauer, Alexander Scheffold, Hans U. Scherer, Matthias Schiemann, Frank A. Schildberg, Kilian Schober, Janina Schoen, Wolfgang Schuh, Thomas Schüler, Axel R. Schulz, Sebastian Schulz, Julia Schulze, Sonia Simonetti, Jeeshan Singh, Katarzyna M. Sitnik, Regina Stark, Sarah Starossom, Christina Stehle, Franziska Szelinski, Leonard Tan, Attila Tarnok, Julia Tornack, Timothy I. M. Tree, Jasper J. P. van Beek, Willem van de Veen, Klaas van Gisbergen, Chiara Vasco, Nikita A. Verheyden, Anouk von Borstel, Kirsten A. Ward‐Hartstonge, Klaus Warnatz, Claudia Waskow, Annika Wiedemann, Anneke Wilharm, James Wing, Oliver Wirz, Jens Wittner, Jennie H. M. Yang, Juhao Yang, Rolf M. Schwiete Foundation, Associazione Italiana per la Ricerca sul Cancro, German Research Foundation, National Institutes of Health (US), European Commission, AII - Inflammatory diseases, Cossarizza, A, Chang, H, Radbruch, A, Abrignani, S, Addo, R, Akdis, M, Andra, I, Andreata, F, Annunziato, F, Arranz, E, Bacher, P, Bari, S, Barnaba, V, Barros-Martins, J, Baumjohann, D, Beccaria, C, Bernardo, D, Boardman, D, Borger, J, Bottcher, C, Brockmann, L, Burns, M, Busch, D, Cameron, G, Cammarata, I, Cassotta, A, Chang, Y, Chirdo, F, Christakou, E, Cicin-Sain, L, Cook, L, Corbett, A, Cornelis, R, Cosmi, L, Davey, M, De Biasi, S, De Simone, G, del Zotto, G, Delacher, M, Di Rosa, F, Santo, J, Diefenbach, A, Dong, J, Dorner, T, Dress, R, Dutertre, C, Eckle, S, Eede, P, Evrard, M, Falk, C, Feuerer, M, Fillatreau, S, Fiz-Lopez, A, Follo, M, Foulds, G, Frobel, J, Gagliani, N, Galletti, G, Gangaev, A, Garbi, N, Garrote, J, Geginat, J, Gherardin, N, Gibellini, L, Ginhoux, F, Godfrey, D, Gruarin, P, Haftmann, C, Hansmann, L, Harpur, C, Hayday, A, Heine, G, Hernandez, D, Herrmann, M, Hoelsken, O, Huang, Q, Huber, S, Huber, J, Huehn, J, Hundemer, M, Hwang, W, Iannacone, M, Ivison, S, Jack, H, Jani, P, Keller, B, Kessler, N, Ketelaars, S, Knop, L, Knopf, J, Koay, H, Kobow, K, Kriegsmann, K, Kristyanto, H, Krueger, A, Kuehne, J, Kunze-Schumacher, H, Kvistborg, P, Kwok, I, Latorre, D, Lenz, D, Levings, M, Lino, A, Liotta, F, Long, H, Lugli, E, Macdonald, K, Maggi, L, Maini, M, Mair, F, Manta, C, Manz, R, Mashreghi, M, Mazzoni, A, Mccluskey, J, Mei, H, Melchers, F, Melzer, S, Mielenz, D, Monin, L, Moretta, L, Multhoff, G, Munoz, L, Munoz-Ruiz, M, Muscate, F, Natalini, A, Neumann, K, Ng, L, Niedobitek, A, Niemz, J, Almeida, L, Notarbartolo, S, Ostendorf, L, Pallett, L, Patel, A, Percin, G, Peruzzi, G, Pinti, M, Pockley, A, Pracht, K, Prinz, I, Pujol-Autonell, I, Pulvirenti, N, Quatrini, L, Quinn, K, Radbruch, H, Rhys, H, Rodrigo, M, Romagnani, C, Saggau, C, Sakaguchi, S, Sallusto, F, Sanderink, L, Sandrock, I, Schauer, C, Scheffold, A, Scherer, H, Schiemann, M, Schildberg, F, Schober, K, Schoen, J, Schuh, W, Schuler, T, Schulz, A, Schulz, S, Schulze, J, Simonetti, S, Singh, J, Sitnik, K, Stark, R, Starossom, S, Stehle, C, Szelinski, F, Tan, L, Tarnok, A, Tornack, J, Tree, T, van Beek, J, van de Veen, W, van Gisbergen, K, Vasco, C, Verheyden, N, von Borstel, A, Ward-Hartstonge, K, Warnatz, K, Waskow, C, Wiedemann, A, Wilharm, A, Wing, J, Wirz, O, Wittner, J, Yang, J, Publica, Cossarizza, A., Chang, H. -D., Radbruch, A., Abrignani, S., Addo, R., Akdis, M., Andra, I., Andreata, F., Annunziato, F., Arranz, E., Bacher, P., Bari, S., Barnaba, V., Barros-Martins, J., Baumjohann, D., Beccaria, C. G., Bernardo, D., Boardman, D. A., Borger, J., Bottcher, C., Brockmann, L., Burns, M., Busch, D. H., Cameron, G., Cammarata, I., Cassotta, A., Chang, Y., Chirdo, F. G., Christakou, E., Cicin-Sain, L., Cook, L., Corbett, A. J., Cornelis, R., Cosmi, L., Davey, M. S., De Biasi, S., De Simone, G., del Zotto, G., Delacher, M., Di Rosa, F., Santo, J. D., Diefenbach, A., Dong, J., Dorner, T., Dress, R. J., Dutertre, C. -A., Eckle, S. B. G., Eede, P., Evrard, M., Falk, C. S., Feuerer, M., Fillatreau, S., Fiz-Lopez, A., Follo, M., Foulds, G. A., Frobel, J., Gagliani, N., Galletti, G., Gangaev, A., Garbi, N., Garrote, J. A., Geginat, J., Gherardin, N. A., Gibellini, L., Ginhoux, F., Godfrey, D. I., Gruarin, P., Haftmann, C., Hansmann, L., Harpur, C. M., Hayday, A. C., Heine, G., Hernandez, D. C., Herrmann, M., Hoelsken, O., Huang, Q., Huber, S., Huber, J. E., Huehn, J., Hundemer, M., Hwang, W. Y. K., Iannacone, M., Ivison, S. M., Jack, H. -M., Jani, P. K., Keller, B., Kessler, N., Ketelaars, S., Knop, L., Knopf, J., Koay, H. -F., Kobow, K., Kriegsmann, K., Kristyanto, H., Krueger, A., Kuehne, J. F., Kunze-Schumacher, H., Kvistborg, P., Kwok, I., Latorre, D., Lenz, D., Levings, M. K., Lino, A. C., Liotta, F., Long, H. M., Lugli, E., Macdonald, K. N., Maggi, L., Maini, M. K., Mair, F., Manta, C., Manz, R. A., Mashreghi, M. -F., Mazzoni, A., Mccluskey, J., Mei, H. E., Melchers, F., Melzer, S., Mielenz, D., Monin, L., Moretta, L., Multhoff, G., Munoz, L. E., Munoz-Ruiz, M., Muscate, F., Natalini, A., Neumann, K., Ng, L. G., Niedobitek, A., Niemz, J., Almeida, L. N., Notarbartolo, S., Ostendorf, L., Pallett, L. J., Patel, A. A., Percin, G. I., Peruzzi, G., Pinti, M., Pockley, A. G., Pracht, K., Prinz, I., Pujol-Autonell, I., Pulvirenti, N., Quatrini, L., Quinn, K. M., Radbruch, H., Rhys, H., Rodrigo, M. B., Romagnani, C., Saggau, C., Sakaguchi, S., Sallusto, F., Sanderink, L., Sandrock, I., Schauer, C., Scheffold, A., Scherer, H. U., Schiemann, M., Schildberg, F. A., Schober, K., Schoen, J., Schuh, W., Schuler, T., Schulz, A. R., Schulz, S., Schulze, J., Simonetti, S., Singh, J., Sitnik, K. M., Stark, R., Starossom, S., Stehle, C., Szelinski, F., Tan, L., Tarnok, A., Tornack, J., Tree, T. I. M., van Beek, J. J. P., van de Veen, W., van Gisbergen, K., Vasco, C., Verheyden, N. A., von Borstel, A., Ward-Hartstonge, K. A., Warnatz, K., Waskow, C., Wiedemann, A., Wilharm, A., Wing, J., Wirz, O., Wittner, J., Yang, J. H. M., and Yang, J.

Subjects
Immunology, citometry, Flow Cytometry, Infections, ddc, Autoimmune Diseases, Animals, Chronic Disease, Humans, Mice, Neoplasms, Practice Guidelines as Topic, Immunology and Allergy, ddc:610, Function and Dysfunction of the Nervous System, guideline
Abstract

© 2021 The Authors., The third edition of Flow Cytometry Guidelines provides the key aspects to consider when performing flow cytometry experiments and includes comprehensive sections describing phenotypes and functional assays of all major human and murine immune cell subsets. Notably, the Guidelines contain helpful tables highlighting phenotypes and key differences between human and murine cells. Another useful feature of this edition is the flow cytometry analysis of clinical samples with examples of flow cytometry applications in the context of autoimmune diseases, cancers as well as acute and chronic infectious diseases. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid. All sections are written and peer-reviewed by leading flow cytometry experts and immunologists, making this edition an essential and state-of-the-art handbook for basic and clinical researchers., Hyun-Dong Chang is supported by the Dr. Rolf M. Schwiete Foundation. Susanne Melzer and Attila Tarnok thank De Novo Software for providing FCS Express. Enrico Lugli is supported by a grant from the Associazione Italiana per la Ricerca sul Cancro (AIRC IG20676). Gabriele De Simone and Giovanni Galletti were supported by Fellowships from the Fondazione Italiana per la Ricerca sul Cancro-Associazione Italiana per la Ricerca sul Cancro (FIRC-AIRC). Jun Dong is supported by Deutsche Forschungsgemeinschft (DFG, German Research Foundation) Projektnummer 389687267 and Chinesisch-Deutsches Zentrum für Wissenschaftsförderung [Sino-German Center for Research Promotion (SGC)] grant C-0072. Nicola Gagliani, Samuel Huber and Franziska Muscate are supported by DFG fundings: SFB841,GA 2441/3-1, HU 1714/10-1. The tetramer APC-conjugated H-2K (d) HIV-1 gag197-205 AMQMLKETI used in TDS assay for mouse blood T cells was obtained through the NIH Tetramer Facility. Larissa Nogueira Almeida was supported by DFG research grant MA 2273/14-1. Supported by the following grants: AIRC 5X1000 2018 id. 21147 (Lorenzo Moretta); AIRC IG 2017 id. 19920 (Lorenzo Moretta); RC-2020 OPBG (Lorenzo Moretta); AIRC and European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 800924 (Linda Quatrini). Dirk Baumjohann was supported by Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Emmy Noether Programme BA 5132/1-2 (252623821) and Germany's Excellence Strategy EXC2151 (390873048).

Published
2021

14. Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)

Author

Lara Gibellini, Sussan Nourshargh, Susanna Cardell, Wlodzimierz Maslinski, Mar Felipo-Benavent, Florian Mair, Hans-Martin Jäck, Lilly Lopez, Klaus Warnatz, John Trowsdale, Diana Ordonez, Marcus Eich, William Hwang, Anne Cooke, Dirk Mielenz, Alberto Orfao, Winfried F. Pickl, Vladimir Benes, Alice Yue, T. Vincent Shankey, Maria Tsoumakidou, Virginia Litwin, Gelo Victoriano Dela Cruz, Andrea Cavani, Sara De Biasi, Larissa Nogueira Almeida, Jonathan J M Landry, Claudia Haftmann, Charlotte Esser, Ana Cumano, Anneke Wilharm, Francesco Dieli, Rudi Beyaert, Alessio Mazzoni, Burkhard Ludewig, Carlo Pucillo, Dirk H. Busch, Joe Trotter, Stipan Jonjić, Marc Veldhoen, Josef Spidlen, Aja M. Rieger, Dieter Adam, Srijit Khan, Todd A. Fehniger, Giuseppe Matarese, Maximilien Evrard, Christian Maueröder, Steffen Schmitt, Kristin A. Hogquist, Barry Moran, Raghavendra Palankar, Markus Feuerer, S Schmid, Susann Rahmig, Amy E. Lovett-Racke, James V. Watson, Megan K. Levings, Susanne Melzer, Dinko Pavlinic, Christopher M. Harpur, Christina Stehle, A. Graham Pockley, Toshinori Nakayama, Attila Tárnok, Juhao Yang, Michael Lohoff, Paulo Vieira, Francisco Sala-de-Oyanguren, Christian Kurts, Anastasia Gangaev, Alfonso Blanco, Hans Scherer, Regine J. Dress, Bruno Silva-Santos, Kiyoshi Takeda, Bimba F. Hoyer, Ilenia Cammarata, Daryl Grummitt, Isabel Panse, Günnur Deniz, Bianka Baying, Friederike Ebner, Esther Schimisky, Leo Hansmann, Thomas Kamradt, Edwin van der Pol, Daniel Scott-Algara, Anna Iannone, Giorgia Alvisi, Sebastian R. Schulz, Francesco Liotta, Irmgard Förster, Beatriz Jávega, Hans-Peter Rahn, Caetano Reis e Sousa, Livius Penter, Xuetao Cao, David P. Sester, Keisuke Goda, Peter Wurst, Iain B. McInnes, Ricardo T. Gazzinelli, Federica Piancone, Gerald Willimsky, Yotam Raz, Pärt Peterson, Wolfgang Fritzsche, Yvonne Samstag, Martin Büscher, Thomas Schüler, Susanne Hartmann, Robert J. Wilkinson, Anna E. S. Brooks, Steven L. C. Ketelaars, Catherine Sautès-Fridman, Anna Rubartelli, Petra Bacher, Katja Kobow, Marco A. Cassatella, Andrea Hauser, Henrik E. Mei, Kilian Schober, Silvia Della Bella, Graham Anderson, Michael D. Ward, Garth Cameron, Sebastian Lunemann, Katharina Kriegsmann, Katarzyna M. Sitnik, Brice Gaudilliere, Chantip Dang-Heine, Marcello Pinti, Paul Klenerman, Frank A. Schildberg, Joana Barros-Martins, Laura G. Rico, Hanlin Zhang, Christian Münz, Thomas Dörner, Jakob Zimmermann, Andrea M. Cooper, Jonni S. Moore, Andreas Diefenbach, Yanling Liu, Wolfgang Bauer, Tobit Steinmetz, Katharina Pracht, Leonard Tan, Peter K. Jani, Alan M. Stall, Petra Hoffmann, Christine S. Falk, Jasmin Knopf, Simon Fillatreau, Hans-Dieter Volk, Luis E. Muñoz, David L. Haviland, William W. Agace, Jonathan Rebhahn, Ljiljana Cvetkovic, Mohamed Trebak, Jordi Petriz, Mario Clerici, Diether J. Recktenwald, Anders Ståhlberg, Tristan Holland, Helen M. McGuire, Sa A. Wang, Christian Kukat, Thomas Kroneis, Laura Cook, Wan Ting Kong, Xin M. Wang, Britta Engelhardt, Pierre Coulie, Genny Del Zotto, Sally A. Quataert, Kata Filkor, Gabriele Multhoff, Bartek Rajwa, Federica Calzetti, Hans Minderman, Cosima T. Baldari, Jens Geginat, Hervé Luche, Gert Van Isterdael, Linda Schadt, Sophia Urbanczyk, Giovanna Borsellino, Liping Yu, Dale I. Godfrey, Achille Anselmo, Rachael C. Walker, Andreas Grützkau, David W. Hedley, Birgit Sawitzki, Silvia Piconese, Maria Yazdanbakhsh, Burkhard Becher, Ramon Bellmas Sanz, Michael Delacher, Hyun-Dong Chang, Immanuel Andrä, Hans-Gustaf Ljunggren, José-Enrique O'Connor, Ahad Khalilnezhad, Sharon Sanderson, Federico Colombo, Götz R. A. Ehrhardt, Inga Sandrock, Enrico Lugli, Christian Bogdan, James B. Wing, Susann Müller, Tomohiro Kurosaki, Derek Davies, Ester B. M. Remmerswaal, Kylie M. Quinn, Christopher A. Hunter, Andreas Radbruch, Timothy P. Bushnell, Anna Erdei, Sabine Adam-Klages, Pascale Eede, Van Duc Dang, Rieke Winkelmann, Thomas Korn, Gemma A. Foulds, Dirk Baumjohann, Matthias Schiemann, Manfred Kopf, Jan Kisielow, Lisa Richter, Jochen Huehn, Gloria Martrus, Alexander Scheffold, Jessica G. Borger, Sidonia B G Eckle, John Bellamy Foster, Anna Katharina Simon, Alicia Wong, Mübeccel Akdis, Gisa Tiegs, Toralf Kaiser, James McCluskey, Anna Vittoria Mattioli, Aaron J. Marshall, Hui-Fern Koay, Eva Orlowski-Oliver, Anja E. Hauser, J. Paul Robinson, Jay K. Kolls, Luca Battistini, Mairi McGrath, Jane L. Grogan, Natalio Garbi, Timothy Tree, Kingston H. G. Mills, Stefan H. E. Kaufmann, Wolfgang Schuh, Ryan R. Brinkman, Tim R. Mosmann, Vincenzo Barnaba, Andreas Dolf, Lorenzo Cosmi, Bo Huang, Andreia C. Lino, Baerbel Keller, René A. W. van Lier, Alexandra J. Corbett, Paul S. Frenette, Pleun Hombrink, Helena Radbruch, Sofie Van Gassen, Olivier Lantz, Lorenzo Moretta, Désirée Kunkel, Kirsten A. Ward-Hartstonge, Armin Saalmüller, Leslie Y. T. Leung, Salvador Vento-Asturias, Paola Lanuti, Alicia Martínez-Romero, Sarah Warth, Zhiyong Poon, Diana Dudziak, Andrea Cossarizza, Kovit Pattanapanyasat, Konrad von Volkmann, Jessica P. Houston, Agnès Lehuen, Andrew Filby, Pratip K. Chattopadhyay, Stefano Casola, Annika Wiedemann, Hannes Stockinger, Jürgen Ruland, Arturo Zychlinsky, Claudia Waskow, Katrin Neumann, Ari Waisman, Lucienne Chatenoud, Sudipto Bari, Kamran Ghoreschi, David W. Galbraith, Yvan Saeys, Hamida Hammad, Andrea Gori, Miguel López-Botet, Gabriel Núñez, Sabine Ivison, Michael Hundemer, Dorothea Reimer, Mark C. Dessing, Günter J. Hämmerling, Rudolf A. Manz, Tomas Kalina, Jonas Hahn, Holden T. Maecker, Hendy Kristyanto, Martin S. Davey, Henning Ulrich, Michael L. Dustin, Takashi Saito, Yousuke Takahama, Milena Nasi, Johanna Huber, Jürgen Wienands, Paolo Dellabona, Andreas Schlitzer, Michael D. Leipold, Kerstin H. Mair, Christian Peth, Immo Prinz, Chiara Romagnani, José M. González-Navajas, Josephine Schlosser, Marina Saresella, Matthias Edinger, Dirk Brenner, Nicole Baumgarth, Rikard Holmdahl, Fang-Ping Huang, Guadalupe Herrera, Malte Paulsen, Gergely Toldi, Luka Cicin-Sain, Reiner Schulte, Christina E. Zielinski, Thomas Winkler, Christoph Goettlinger, Philip E. Boulais, Jennie H M Yang, Antonio Celada, Heike Kunze-Schumacher, Julia Tornack, Florian Ingelfinger, Jenny Mjösberg, Andy Riddell, Leonie Wegener, Thomas Höfer, Christoph Hess, James P. Di Santo, Anna E. Oja, J. Kühne, Willem van de Veen, Mary Bebawy, Alberto Mantovani, Bart Everts, Giovanna Lombardi, Laura Maggi, Anouk von Borstel, Pia Kvistborg, Elisabetta Traggiai, A Ochel, Nima Aghaeepour, Charles-Antoine Dutertre, Matthieu Allez, Thomas Höllt, Wenjun Ouyang, Regina Stark, Maries van den Broek, Shimon Sakaguchi, Paul K. Wallace, Silvano Sozzani, Francesca LaRosa, Annette Oxenius, Malgorzata J. Podolska, Ivana Marventano, Wilhelm Gerner, Oliver F. Wirz, Britta Frehse, Gevitha Ravichandran, Martin Herrmann, Carl S. Goodyear, Gary Warnes, Helen Ferry, Stefan Frischbutter, Tim R. Radstake, Salomé LeibundGut-Landmann, Yi Zhao, Axel Schulz, Angela Santoni, Pablo Engel, Daniela C. Hernández, Andreas Acs, Cristiano Scottà, Francesco Annunziato, Thomas Weisenburger, Wolfgang Beisker, Sue Chow, Fritz Melchers, Daniel E. Speiser, Immanuel Kwok, Florent Ginhoux, Dominic A. Boardman, Natalie Stanley, Carsten Watzl, Marie Follo, Erik Lubberts, Andreas Krueger, Susanne Ziegler, Göran K. Hansson, David Voehringer, Antonia Niedobitek, Eleni Christakou, Lai Guan Ng, Sabine Baumgart, Nicholas A Gherardin, Antonio Cosma, Orla Maguire, Jolene Bradford, Daniel Schraivogel, Linda Quatrini, Stephen D. Miller, Rheumatology, Università degli Studi di Modena e Reggio Emilia (UNIMORE), Deutsches Rheuma-ForschungsZentrum (DRFZ), Deutsches Rheuma-ForschungsZentrum, Swiss Institute of Allergy and Asthma Research (SIAF), Universität Zürich [Zürich] = University of Zurich (UZH), Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université de Paris (UP), Ecotaxie, microenvironnement et développement lymphocytaire (EMily (UMR_S_1160 / U1160)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Department of Internal Medicine, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI)-DENOTHE Center, Institute of Clinical Molecular Biology, Kiel University, Department of Life Sciences [Siena, Italy], Università degli Studi di Siena = University of Siena (UNISI), Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP), Dulbecco Telethon Institute/Department of Biology, Caprotec Bioanalytics GmbH, International Occultation Timing Association European Section (IOTA ES), International Occultation Timing Association European Section, European Molecular Biology Laboratory [Heidelberg] (EMBL), VIB-UGent Center for Inflammation Research [Gand, Belgique] (IRC), VIB [Belgium], Fondazione Santa Lucia (IRCCS), Department of Immunology, Chinese Academy of Medical Sciences, FIRC Institute of Molecular Oncology Foundation, IFOM, Istituto FIRC di Oncologia Molecolare (IFOM), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Physiopatology and Transplantation, University of Milan (DEPT), University of Milan, Monash University [Clayton], Institut des Maladies Emergentes et des Thérapies Innovantes (IMETI), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institute of Cellular Pathology, Université Catholique de Louvain = Catholic University of Louvain (UCL), Lymphopoïèse (Lymphopoïèse (UMR_1223 / U1223 / U-Pasteur_4)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Experimental Immunology Unit, Dept. of Oncology, DIBIT San Raffaele Scientific Institute, Immunité Innée - Innate Immunity, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Biopharmacy [Bruxelles, Belgium] (Institute for Medical Immunology IMI), Université libre de Bruxelles (ULB), Charité Hospital, Humboldt-Universität zu Berlin, Agency for science, technology and research [Singapore] (A*STAR), Laboratory of Molecular Immunology and the Howard Hughes Institute, Rockefeller University [New York], Kennedy Institute of Rheumatology [Oxford, UK], Imperial College London, Theodor Kocher Institute, University of Bern, Leibniz Research Institute for Environmental Medicine [Düsseldorf, Germany] ( IUF), Université Lumière - Lyon 2 (UL2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), University of Edinburgh, Integrative Biology Program [Milano], Istituto Nazionale Genetica Molecolare [Milano] (INGM), Singapore Immunology Network (SIgN), Biomedical Sciences Institute (BMSI), Universitat de Barcelona (UB), Rheumatologie, Cell Biology, Department of medicine [Stockholm], Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm], Department for Internal Medicine 3, Institute for Clinical Immunology, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Delft University of Technology (TU Delft), Medical Inflammation Research, Karolinska Institutet [Stockholm], Department of Photonics Engineering [Lyngby], Technical University of Denmark [Lyngby] (DTU), Dpt of Experimental Immunology [Braunschweig], Helmholtz Centre for Infection Research (HZI), Department of Internal Medicine V, Universität Heidelberg [Heidelberg], Department of Histology and Embryology, University of Rijeka, Freiburg University Medical Center, Nuffield Dept of Clinical Medicine, University of Oxford [Oxford]-NIHR Biomedical Research Centre, Institute of Integrative Biology, Molecular Biomedicine, Berlin Institute of Health (BIH), Laboratory for Lymphocyte Differentiation, RIKEN Research Center, Institutes of Molecular Medicine and Experimental Immunology, University of Bonn, Immunité et cancer (U932), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Department of Surgery [Vancouver, BC, Canada] (Child and Family Research Institute), University of British Columbia (UBC)-Child and Family Research Institute [Vancouver, BC, Canada], College of Food Science and Technology [Shangai], Shanghai Ocean University, Institute for Medical Microbiology and Hygiene, University of Marburg, King‘s College London, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Centre d'Immunophénomique (CIPHE), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Brustzentrum Kantonsspital St. Gallen, Immunotechnology Section, Vaccine Research Center, National Institutes of Health [Bethesda] (NIH)-National Institute of Allergy and Infectious Diseases, Heinrich Pette Institute [Hamburg], Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Department of Immunology and Cell Biology, Mario Negri Institute, Laboratory of Molecular Medicine and Biotechnology, Don C. Gnocchi ONLUS Foundation, Institute of Translational Medicine, Klinik für Dermatologie, Venerologie und Allergologie, School of Biochemistry and Immunology, Department of Medicine Huddinge, Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm]-Lipid Laboratory, Università di Genova, Dipartimento di Medicina Sperimentale, Department of Environmental Microbiology, Helmholtz Zentrum für Umweltforschung = Helmholtz Centre for Environmental Research (UFZ), Department of Radiation Oncology [Munich], Ludwig-Maximilians-Universität München (LMU), Centre de Recherche Publique- Santé, Université du Luxembourg (Uni.lu), William Harvey Research Institute, Barts and the London Medical School, University of Michigan [Ann Arbor], University of Michigan System, Centro de Investigacion del Cancer (CSIC), Universitario de Salamanca, Molecular Pathology [Tartu, Estonia], University of Tartu, Hannover Medical School [Hannover] (MHH), Centre d'Immunologie de Marseille - Luminy (CIML), Monash Biomedicine Discovery Institute, Cytometry Laboratories and School of Veterinary Medicine, Purdue University [West Lafayette], Data Mining and Modelling for Biomedicine [Ghent, Belgium], VIB Center for Inflammation Research [Ghent, Belgium], Laboratory for Cell Signaling, RIKEN Research Center for Allergy and Immunology, RIKEN Research Center for Allergy and Immunology, Osaka University [Osaka], Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Institute of Medical Immunology [Berlin, Germany], FACS and Array Core Facility, Johannes Gutenberg - Universität Mainz (JGU), Otto-von-Guericke University [Magdeburg] (OVGU), SUPA School of Physics and Astronomy [University of St Andrews], University of St Andrews [Scotland]-Scottish Universities Physics Alliance (SUPA), Biologie Cellulaire des Lymphocytes - Lymphocyte Cell Biology, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), General Pathology and Immunology (GPI), University of Brescia, Université de Lausanne (UNIL), Terry Fox Laboratory, BC Cancer Agency (BCCRC)-British Columbia Cancer Agency Research Centre, Department of Molecular Immunology, Medizinische Universität Wien = Medical University of Vienna, Dept. Pediatric Cardiology, Universität Leipzig [Leipzig], Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Center for Cardiovascular Sciences, Albany Medical College, Dept Pathol, Div Immunol, University of Cambridge [UK] (CAM), Department of Information Technology [Gent], Universiteit Gent, Department of Plant Systems Biology, Department of Plant Biotechnology and Genetics, Universiteit Gent = Ghent University [Belgium] (UGENT), Division of Molecular Immunology, Institute for Immunology, Department of Geological Sciences, University of Oregon [Eugene], Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention, University of Colorado [Colorado Springs] (UCCS), FACS laboratory, Cancer Research, London, Cancer Research UK, Regeneration in Hematopoiesis and Animal Models of Hematopoiesis, Faculty of Medicine, Dresden University of Technology, Barbara Davis Center for Childhood Diabetes (BDC), University of Colorado Anschutz [Aurora], School of Computer and Electronic Information [Guangxi University], Guangxi University [Nanning], School of Materials Science and Engineering, Nanyang Technological University [Singapour], Max Planck Institute for Infection Biology (MPIIB), Max-Planck-Gesellschaft, Work in the laboratory of Dieter Adam is supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—Projektnummer 125440785 – SFB 877, Project B2.Petra Hoffmann, Andrea Hauser, and Matthias Edinger thank BD Biosciences®, San José, CA, USA, and SKAN AG, Bale, Switzerland for fruitful cooperation during the development, construction, and installation of the GMP‐compliant cell sorting equipment and the Bavarian Immune Therapy Network (BayImmuNet) for financial support.Edwin van der Pol and Paola Lanuti acknowledge Aleksandra Gąsecka M.D. for excellent experimental support and Dr. Rienk Nieuwland for textual suggestions. This work was supported by the Netherlands Organisation for Scientific Research – Domain Applied and Engineering Sciences (NWO‐TTW), research program VENI 15924.Jessica G Borger, Kylie M Quinn, Mairi McGrath, and Regina Stark thank Francesco Siracusa and Patrick Maschmeyer for providing data.Larissa Nogueira Almeida was supported by DFG research grant MA 2273/14‐1. Rudolf A. Manz was supported by the Excellence Cluster 'Inflammation at Interfaces' (EXC 306/2).Susanne Hartmann and Friederike Ebner were supported by the German Research Foundation (GRK 2046).Hans Minderman was supported by NIH R50CA211108.This work was funded by the Deutsche Forschungsgemeinschaft through the grant TRR130 (project P11 and C03) to Thomas H. Winkler.Ramon Bellmàs Sanz, Jenny Kühne, and Christine S. Falk thank Jana Keil and Kerstin Daemen for excellent technical support. The work was funded by the Germany Research Foundation CRC738/B3 (CSF).The work by the Mei laboratory was supported by German Research Foundation Grant ME 3644/5‐1 and TRR130 TP24, the German Rheumatism Research Centre Berlin, European Union Innovative Medicines Initiative ‐ Joint Undertaking ‐ RTCure Grant Agreement 777357, the Else Kröner‐Fresenius‐Foundation, German Federal Ministry of Education and Research e:Med sysINFLAME Program Grant 01ZX1306B and KMU‐innovativ 'InnoCyt', and the Leibniz Science Campus for Chronic Inflammation (http://www.chronische-entzuendung.org).Axel Ronald Schulz, Antonio Cosma, Sabine Baumgart, Brice Gaudilliere, Helen M. McGuire, and Henrik E. Mei thank Michael D. Leipold for critically reading the manuscript.Christian Kukat acknowledges support from the ISAC SRL Emerging Leaders program.John Trowsdale received funding from the European Research Council under the European Union's Horizon 2020 research and innovation program (Grant Agreement 695551)., European Project: 7728036(1978), Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Università degli Studi di Firenze = University of Florence (UniFI)-DENOTHE Center, Università degli Studi di Milano = University of Milan (UNIMI), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Humboldt University Of Berlin, Leibniz Research Institute for Environmental Medicine [Düsseldorf, Germany] (IUF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Universität Heidelberg [Heidelberg] = Heidelberg University, Universitäts Klinikum Freiburg = University Medical Center Freiburg (Uniklinik), University of Oxford-NIHR Biomedical Research Centre, Universität Bonn = University of Bonn, Università degli Studi di Firenze = University of Florence (UniFI), Università degli studi di Genova = University of Genoa (UniGe), Universidad de Salamanca, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Otto-von-Guericke-Universität Magdeburg = Otto-von-Guericke University [Magdeburg] (OVGU), Université de Lausanne = University of Lausanne (UNIL), Universität Leipzig, Universiteit Gent = Ghent University (UGENT), HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany., Cossarizza, A., Chang, H. -D., Radbruch, A., Acs, A., Adam, D., Adam-Klages, S., Agace, W. W., Aghaeepour, N., Akdis, M., Allez, M., Almeida, L. N., Alvisi, G., Anderson, G., Andra, I., Annunziato, F., Anselmo, A., Bacher, P., Baldari, C. T., Bari, S., Barnaba, V., Barros-Martins, J., Battistini, L., Bauer, W., Baumgart, S., Baumgarth, N., Baumjohann, D., Baying, B., Bebawy, M., Becher, B., Beisker, W., Benes, V., Beyaert, R., Blanco, A., Boardman, D. A., Bogdan, C., Borger, J. G., Borsellino, G., Boulais, P. E., Bradford, J. A., Brenner, D., Brinkman, R. R., Brooks, A. E. S., Busch, D. H., Buscher, M., Bushnell, T. P., Calzetti, F., Cameron, G., Cammarata, I., Cao, X., Cardell, S. L., Casola, S., Cassatella, M. A., Cavani, A., Celada, A., Chatenoud, L., Chattopadhyay, P. K., Chow, S., Christakou, E., Cicin-Sain, L., Clerici, M., Colombo, F. S., Cook, L., Cooke, A., Cooper, A. M., Corbett, A. J., Cosma, A., Cosmi, L., Coulie, P. G., Cumano, A., Cvetkovic, L., Dang, V. D., Dang-Heine, C., Davey, M. S., Davies, D., De Biasi, S., Del Zotto, G., Dela Cruz, G. V., Delacher, M., Della Bella, S., Dellabona, P., Deniz, G., Dessing, M., Di Santo, J. P., Diefenbach, A., Dieli, F., Dolf, A., Dorner, T., Dress, R. J., Dudziak, D., Dustin, M., Dutertre, C. -A., Ebner, F., Eckle, S. B. G., Edinger, M., Eede, P., Ehrhardt, G. R. A., Eich, M., Engel, P., Engelhardt, B., Erdei, A., Esser, C., Everts, B., Evrard, M., Falk, C. S., Fehniger, T. A., Felipo-Benavent, M., Ferry, H., Feuerer, M., Filby, A., Filkor, K., Fillatreau, S., Follo, M., Forster, I., Foster, J., Foulds, G. A., Frehse, B., Frenette, P. S., Frischbutter, S., Fritzsche, W., Galbraith, D. W., Gangaev, A., Garbi, N., Gaudilliere, B., Gazzinelli, R. T., Geginat, J., Gerner, W., Gherardin, N. A., Ghoreschi, K., Gibellini, L., Ginhoux, F., Goda, K., Godfrey, D. I., Goettlinger, C., Gonzalez-Navajas, J. M., Goodyear, C. S., Gori, A., Grogan, J. L., Grummitt, D., Grutzkau, A., Haftmann, C., Hahn, J., Hammad, H., Hammerling, G., Hansmann, L., Hansson, G., Harpur, C. M., Hartmann, S., Hauser, A., Hauser, A. E., Haviland, D. L., Hedley, D., Hernandez, D. C., Herrera, G., Herrmann, M., Hess, C., Hofer, T., Hoffmann, P., Hogquist, K., Holland, T., Hollt, T., Holmdahl, R., Hombrink, P., Houston, J. P., Hoyer, B. F., Huang, B., Huang, F. -P., Huber, J. E., Huehn, J., Hundemer, M., Hunter, C. A., Hwang, W. Y. K., Iannone, A., Ingelfinger, F., Ivison, S. M., Jack, H. -M., Jani, P. K., Javega, B., Jonjic, S., Kaiser, T., Kalina, T., Kamradt, T., Kaufmann, S. H. E., Keller, B., Ketelaars, S. L. C., Khalilnezhad, A., Khan, S., Kisielow, J., Klenerman, P., Knopf, J., Koay, H. -F., Kobow, K., Kolls, J. K., Kong, W. T., Kopf, M., Korn, T., Kriegsmann, K., Kristyanto, H., Kroneis, T., Krueger, A., Kuhne, J., Kukat, C., Kunkel, D., Kunze-Schumacher, H., Kurosaki, T., Kurts, C., Kvistborg, P., Kwok, I., Landry, J., Lantz, O., Lanuti, P., Larosa, F., Lehuen, A., LeibundGut-Landmann, S., Leipold, M. D., Leung, L. Y. T., Levings, M. K., Lino, A. C., Liotta, F., Litwin, V., Liu, Y., Ljunggren, H. -G., Lohoff, M., Lombardi, G., Lopez, L., Lopez-Botet, M., Lovett-Racke, A. E., Lubberts, E., Luche, H., Ludewig, B., Lugli, E., Lunemann, S., Maecker, H. T., Maggi, L., Maguire, O., Mair, F., Mair, K. H., Mantovani, A., Manz, R. A., Marshall, A. J., Martinez-Romero, A., Martrus, G., Marventano, I., Maslinski, W., Matarese, G., Mattioli, A. V., Maueroder, C., Mazzoni, A., Mccluskey, J., Mcgrath, M., Mcguire, H. M., Mcinnes, I. B., Mei, H. E., Melchers, F., Melzer, S., Mielenz, D., Miller, S. D., Mills, K. H. G., Minderman, H., Mjosberg, J., Moore, J., Moran, B., Moretta, L., Mosmann, T. R., Muller, S., Multhoff, G., Munoz, L. E., Munz, C., Nakayama, T., Nasi, M., Neumann, K., Ng, L. G., Niedobitek, A., Nourshargh, S., Nunez, G., O'Connor, J. -E., Ochel, A., Oja, A., Ordonez, D., Orfao, A., Orlowski-Oliver, E., Ouyang, W., Oxenius, A., Palankar, R., Panse, I., Pattanapanyasat, K., Paulsen, M., Pavlinic, D., Penter, L., Peterson, P., Peth, C., Petriz, J., Piancone, F., Pickl, W. F., Piconese, S., Pinti, M., Pockley, A. G., Podolska, M. J., Poon, Z., Pracht, K., Prinz, I., Pucillo, C. E. M., Quataert, S. A., Quatrini, L., Quinn, K. M., Radbruch, H., Radstake, T. R. D. J., Rahmig, S., Rahn, H. -P., Rajwa, B., Ravichandran, G., Raz, Y., Rebhahn, J. A., Recktenwald, D., Reimer, D., Reis e Sousa, C., Remmerswaal, E. B. M., Richter, L., Rico, L. G., Riddell, A., Rieger, A. M., Robinson, J. P., Romagnani, C., Rubartelli, A., Ruland, J., Saalmuller, A., Saeys, Y., Saito, T., Sakaguchi, S., Sala-de-Oyanguren, F., Samstag, Y., Sanderson, S., Sandrock, I., Santoni, A., Sanz, R. B., Saresella, M., Sautes-Fridman, C., Sawitzki, B., Schadt, L., Scheffold, A., Scherer, H. U., Schiemann, M., Schildberg, F. A., Schimisky, E., Schlitzer, A., Schlosser, J., Schmid, S., Schmitt, S., Schober, K., Schraivogel, D., Schuh, W., Schuler, T., Schulte, R., Schulz, A. R., Schulz, S. R., Scotta, C., Scott-Algara, D., Sester, D. P., Shankey, T. V., Silva-Santos, B., Simon, A. K., Sitnik, K. M., Sozzani, S., Speiser, D. E., Spidlen, J., Stahlberg, A., Stall, A. M., Stanley, N., Stark, R., Stehle, C., Steinmetz, T., Stockinger, H., Takahama, Y., Takeda, K., Tan, L., Tarnok, A., Tiegs, G., Toldi, G., Tornack, J., Traggiai, E., Trebak, M., Tree, T. I. M., Trotter, J., Trowsdale, J., Tsoumakidou, M., Ulrich, H., Urbanczyk, S., van de Veen, W., van den Broek, M., van der Pol, E., Van Gassen, S., Van Isterdael, G., van Lier, R. A. W., Veldhoen, M., Vento-Asturias, S., Vieira, P., Voehringer, D., Volk, H. -D., von Borstel, A., von Volkmann, K., Waisman, A., Walker, R. V., Wallace, P. K., Wang, S. A., Wang, X. M., Ward, M. D., Ward-Hartstonge, K. A., Warnatz, K., Warnes, G., Warth, S., Waskow, C., Watson, J. V., Watzl, C., Wegener, L., Weisenburger, T., Wiedemann, A., Wienands, J., Wilharm, A., Wilkinson, R. J., Willimsky, G., Wing, J. B., Winkelmann, R., Winkler, T. H., Wirz, O. F., Wong, A., Wurst, P., Yang, J. H. M., Yang, J., Yazdanbakhsh, M., Yu, L., Yue, A., Zhang, H., Zhao, Y., Ziegler, S. M., Zielinski, C., Zimmermann, J., Zychlinsky, A., UCL - SSS/DDUV - Institut de Duve, UCL - SSS/DDUV/GECE - Génétique cellulaire, Netherlands Organization for Scientific Research, German Research Foundation, European Commission, European Research Council, Repositório da Universidade de Lisboa, CCA - Imaging and biomarkers, Experimental Immunology, AII - Infectious diseases, AII - Inflammatory diseases, Biomedical Engineering and Physics, ACS - Atherosclerosis & ischemic syndromes, and Landsteiner Laboratory

Subjects
0301 basic medicine, Consensus, Immunology, Consensu, Cell Separation, Biology, Article, Flow cytometry, 03 medical and health sciences, 0302 clinical medicine, Guidelines, Allergy and Immunology, medicine, Cell separation, Immunology and Allergy, Humans, guidelines, flow cytometry, immunology, medicine.diagnostic_test, BIOMEDICINE AND HEALTHCARE. Basic Medical Sciences, Cell sorting, Flow Cytometry, Cell selection, Data science, 3. Good health, 030104 developmental biology, Phenotype, [SDV.IMM]Life Sciences [q-bio]/Immunology, BIOMEDICINA I ZDRAVSTVO. Temeljne medicinske znanosti, 030215 immunology, Human
Abstract

All authors: Andrea Cossarizza Hyun‐Dong Chang Andreas Radbruch Andreas Acs Dieter Adam Sabine Adam‐Klages William W. Agace Nima Aghaeepour Mübeccel Akdis Matthieu Allez Larissa Nogueira Almeida Giorgia Alvisi Graham Anderson Immanuel Andrä Francesco Annunziato Achille Anselmo Petra Bacher Cosima T. Baldari Sudipto Bari Vincenzo Barnaba Joana Barros‐Martins Luca Battistini Wolfgang Bauer Sabine Baumgart Nicole Baumgarth Dirk Baumjohann Bianka Baying Mary Bebawy Burkhard Becher Wolfgang Beisker Vladimir Benes Rudi Beyaert Alfonso Blanco Dominic A. Boardman Christian Bogdan Jessica G. Borger Giovanna Borsellino Philip E. Boulais Jolene A. Bradford Dirk Brenner Ryan R. Brinkman Anna E. S. Brooks Dirk H. Busch Martin Büscher Timothy P. Bushnell Federica Calzetti Garth Cameron Ilenia Cammarata Xuetao Cao Susanna L. Cardell Stefano Casola Marco A. Cassatella Andrea Cavani Antonio Celada Lucienne Chatenoud Pratip K. Chattopadhyay Sue Chow Eleni Christakou Luka Čičin‐Šain Mario Clerici Federico S. Colombo Laura Cook Anne Cooke Andrea M. Cooper Alexandra J. Corbett Antonio Cosma Lorenzo Cosmi Pierre G. Coulie Ana Cumano Ljiljana Cvetkovic Van Duc Dang Chantip Dang‐Heine Martin S. Davey Derek Davies Sara De Biasi Genny Del Zotto Gelo Victoriano Dela Cruz Michael Delacher Silvia Della Bella Paolo Dellabona Günnur Deniz Mark Dessing James P. Di Santo Andreas Diefenbach Francesco Dieli Andreas Dolf Thomas Dörner Regine J. Dress Diana Dudziak Michael Dustin Charles‐Antoine Dutertre Friederike Ebner Sidonia B. G. Eckle Matthias Edinger Pascale Eede Götz R.A. Ehrhardt Marcus Eich Pablo Engel Britta Engelhardt Anna Erdei Charlotte Esser Bart Everts Maximilien Evrard Christine S. Falk Todd A. Fehniger Mar Felipo‐Benavent Helen Ferry Markus Feuerer Andrew Filby Kata Filkor Simon Fillatreau Marie Follo Irmgard Förster John Foster Gemma A. Foulds Britta Frehse Paul S. Frenette Stefan Frischbutter Wolfgang Fritzsche David W. Galbraith Anastasia Gangaev Natalio Garbi Brice Gaudilliere Ricardo T. Gazzinelli Jens Geginat Wilhelm Gerner Nicholas A. Gherardin Kamran Ghoreschi Lara Gibellini Florent Ginhoux Keisuke Goda Dale I. Godfrey Christoph Goettlinger Jose M. González‐Navajas Carl S. Goodyear Andrea Gori Jane L. Grogan Daryl Grummitt Andreas Grützkau Claudia Haftmann Jonas Hahn Hamida Hammad Günter Hämmerling Leo Hansmann Goran Hansson Christopher M. Harpur Susanne Hartmann Andrea Hauser Anja E. Hauser David L. Haviland David Hedley Daniela C. Hernández Guadalupe Herrera Martin Herrmann Christoph Hess Thomas Höfer Petra Hoffmann Kristin Hogquist Tristan Holland Thomas Höllt Rikard Holmdahl Pleun Hombrink Jessica P. Houston Bimba F. Hoyer Bo Huang Fang‐Ping Huang Johanna E. Huber Jochen Huehn Michael Hundemer Christopher A. Hunter William Y. K. Hwang Anna Iannone Florian Ingelfinger Sabine M Ivison Hans‐Martin Jäck Peter K. Jani Beatriz Jávega Stipan Jonjic Toralf Kaiser Tomas Kalina Thomas Kamradt Stefan H. E. Kaufmann Baerbel Keller Steven L. C. Ketelaars Ahad Khalilnezhad Srijit Khan Jan Kisielow Paul Klenerman Jasmin Knopf Hui‐Fern Koay Katja Kobow Jay K. Kolls Wan Ting Kong Manfred Kopf Thomas Korn Katharina Kriegsmann Hendy Kristyanto Thomas Kroneis Andreas Krueger Jenny Kühne Christian Kukat Désirée Kunkel Heike Kunze‐Schumacher Tomohiro Kurosaki Christian Kurts Pia Kvistborg Immanuel Kwok Jonathan Landry Olivier Lantz Paola Lanuti Francesca LaRosa Agnès Lehuen Salomé LeibundGut‐Landmann Michael D. Leipold Leslie Y.T. Leung Megan K. Levings Andreia C. Lino Francesco Liotta Virginia Litwin Yanling Liu Hans‐Gustaf Ljunggren Michael Lohoff Giovanna Lombardi Lilly Lopez Miguel López‐Botet Amy E. Lovett‐Racke Erik Lubberts Herve Luche Burkhard Ludewig Enrico Lugli Sebastian Lunemann Holden T. Maecker Laura Maggi Orla Maguire Florian Mair Kerstin H. Mair Alberto Mantovani Rudolf A. Manz Aaron J. Marshall Alicia Martínez‐Romero Glòria Martrus Ivana Marventano Wlodzimierz Maslinski Giuseppe Matarese Anna Vittoria Mattioli Christian Maueröder Alessio Mazzoni James McCluskey Mairi McGrath Helen M. McGuire Iain B. McInnes Henrik E. Mei Fritz Melchers Susanne Melzer Dirk Mielenz Stephen D. Miller Kingston H.G. Mills Hans Minderman Jenny Mjösberg Jonni Moore Barry Moran Lorenzo Moretta Tim R. Mosmann Susann Müller Gabriele Multhoff Luis Enrique Muñoz Christian Münz Toshinori Nakayama Milena Nasi Katrin Neumann Lai Guan Ng Antonia Niedobitek Sussan Nourshargh Gabriel Núñez José‐Enrique O'Connor Aaron Ochel Anna Oja Diana Ordonez Alberto Orfao Eva Orlowski‐Oliver Wenjun Ouyang Annette Oxenius Raghavendra Palankar Isabel Panse Kovit Pattanapanyasat Malte Paulsen Dinko Pavlinic Livius Penter Pärt Peterson Christian Peth Jordi Petriz Federica Piancone Winfried F. Pickl Silvia Piconese Marcello Pinti A. Graham Pockley Malgorzata Justyna Podolska Zhiyong Poon Katharina Pracht Immo Prinz Carlo E. M. Pucillo Sally A. Quataert Linda Quatrini Kylie M. Quinn Helena Radbruch Tim R. D. J. Radstake Susann Rahmig Hans‐Peter Rahn Bartek Rajwa Gevitha Ravichandran Yotam Raz Jonathan A. Rebhahn Diether Recktenwald Dorothea Reimer Caetano Reis e Sousa Ester B.M. Remmerswaal Lisa Richter Laura G. Rico Andy Riddell Aja M. Rieger J. Paul Robinson Chiara Romagnani Anna Rubartelli Jürgen Ruland Armin Saalmüller Yvan Saeys Takashi Saito Shimon Sakaguchi Francisco Sala‐de‐Oyanguren Yvonne Samstag Sharon Sanderson Inga Sandrock Angela Santoni Ramon Bellmàs Sanz Marina Saresella Catherine Sautes‐Fridman Birgit Sawitzki Linda Schadt Alexander Scheffold Hans U. Scherer Matthias Schiemann Frank A. Schildberg Esther Schimisky Andreas Schlitzer Josephine Schlosser Stephan Schmid Steffen Schmitt Kilian Schober Daniel Schraivogel Wolfgang Schuh Thomas Schüler Reiner Schulte Axel Ronald Schulz Sebastian R. Schulz Cristiano Scottá Daniel Scott‐Algara David P. Sester T. Vincent Shankey Bruno Silva‐Santos Anna Katharina Simon Katarzyna M. Sitnik Silvano Sozzani Daniel E. Speiser Josef Spidlen Anders Stahlberg Alan M. Stall Natalie Stanley Regina Stark Christina Stehle Tobit Steinmetz Hannes Stockinger Yousuke Takahama Kiyoshi Takeda Leonard Tan Attila Tárnok Gisa Tiegs Gergely Toldi Julia Tornack Elisabetta Traggiai Mohamed Trebak Timothy I.M. Tree Joe Trotter John Trowsdale Maria Tsoumakidou Henning Ulrich Sophia Urbanczyk Willem van de Veen Maries van den Broek Edwin van der Pol Sofie Van Gassen Gert Van Isterdael René A.W. van Lier Marc Veldhoen Salvador Vento‐Asturias Paulo Vieira David Voehringer Hans‐Dieter Volk Anouk von Borstel Konrad von Volkmann Ari Waisman Rachael V. Walker Paul K. Wallace Sa A. Wang Xin M. Wang Michael D. Ward Kirsten A Ward‐Hartstonge Klaus Warnatz Gary Warnes Sarah Warth Claudia Waskow James V. Watson Carsten Watzl Leonie Wegener Thomas Weisenburger Annika Wiedemann Jürgen Wienands Anneke Wilharm Robert John Wilkinson Gerald Willimsky James B. Wing Rieke Winkelmann Thomas H. Winkler Oliver F. Wirz Alicia Wong Peter Wurst Jennie H. M. Yang Juhao Yang Maria Yazdanbakhsh Liping Yu Alice Yue Hanlin Zhang Yi Zhao Susanne Maria Ziegler Christina Zielinski Jakob Zimmermann Arturo Zychlinsky., These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer‐reviewed by leading experts in the field, making this an essential research companion., This work was supported by the Netherlands Organisation for Scientific Research – Domain Applied and Engineering Sciences (NWO-TTW), research program VENI 15924. This work was funded by the Deutsche Forschungsgemeinschaft. European Union Innovative Medicines Initiative - Joint Undertaking - RTCure Grant Agreement 777357 and innovation program (Grant Agreement 695551).

Published
2019

15. FOXP3 snatches transcription factors depending on the context.

Author

Schmidleithner L, Stüve P, and Feuerer M

Subjects
Humans, Animals, Gene Expression Regulation, DNA-Binding Proteins metabolism, DNA-Binding Proteins genetics, Transcription Factors metabolism, Transcription Factors genetics, Forkhead Transcription Factors metabolism, Forkhead Transcription Factors genetics, T-Lymphocytes, Regulatory immunology, T-Lymphocytes, Regulatory metabolism
Abstract

FOXP3 hijacks DNA-binding proteins to regulate gene expression. In this issue of JEM, He et al. (https://doi.org/10.1084/jem.20232068) propose a dynamic model in which FOXP3 associates with DNA-binding proteins to regulate Treg cell function in response to environmental cues., (© 2024 Schmidleithner et al.)

Published
2024
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16. Single-cell chromatin accessibility and transposable element landscapes reveal shared features of tissue-residing immune cells.

Author

Simon M, Stüve P, Schmidleithner L, Bittner S, Beumer N, Strieder N, Schmidl C, Pant A, Gebhard C, Eigenberger A, Rehli M, Prantl L, Hehlgans T, Brors B, Imbusch CD, Delacher M, and Feuerer M

Subjects
Animals, Mice, Organ Specificity genetics, Transcription Factors metabolism, Transcription Factors genetics, Mice, Inbred C57BL, Humans, Chromatin metabolism, Chromatin genetics, T-Lymphocytes, Regulatory immunology, DNA Transposable Elements genetics, Single-Cell Analysis
Abstract

Tissue adaptation is required for regulatory T (Treg) cell function within organs. Whether this program shares aspects with other tissue-localized immune populations is unclear. Here, we analyzed single-cell chromatin accessibility data, including the transposable element (TE) landscape of CD45 + immune cells from colon, skin, adipose tissue, and spleen. We identified features of organ-specific tissue adaptation across different immune cells. Focusing on tissue Treg cells, we found conservation of the Treg tissue adaptation program in other tissue-localized immune cells, such as amphiregulin-producing T helper (Th)17 cells. Accessible TEs can act as regulatory elements, but their contribution to tissue adaptation is not understood. TE landscape analysis revealed an enrichment of specific transcription factor binding motifs in TE regions within accessible chromatin peaks. TEs, specifically from the LTR family, were located in enhancer regions and associated with tissue adaptation. These findings broaden our understanding of immune tissue residency and provide an important step toward organ-specific immune interventions., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Published
2024
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17. The effector program of human CD8 T cells supports tissue remodeling.

Author

Delacher M, Schmidleithner L, Simon M, Stüve P, Sanderink L, Hotz-Wagenblatt A, Wuttke M, Schambeck K, Ruhland B, Hofmann V, Bittner S, Ritter U, Pant A, Helbich SS, Voss M, Lemmermann NA, Bessiri-Schake L, Bohn T, Eigenberger A, Menevse AN, Gebhard C, Strieder N, Abken H, Rehli M, Huehn J, Beckhove P, Hehlgans T, Junger H, Geissler EK, Prantl L, Werner JM, Schmidl C, Brors B, Imbusch CD, and Feuerer M

Subjects
Humans, ErbB Receptors, Adipose Tissue, Cell Cycle, CD8-Positive T-Lymphocytes, T-Lymphocytes, Cytotoxic
Abstract

CD8 T lymphocytes are classically viewed as cytotoxic T cells. Whether human CD8 T cells can, in parallel, induce a tissue regeneration program is poorly understood. Here, antigen-specific assay systems revealed that human CD8 T cells not only mediated cytotoxicity but also promoted tissue remodeling. Activated CD8 T cells could produce the epidermal growth factor receptor (EGFR)-ligand amphiregulin (AREG) and sensitize epithelial cells for enhanced regeneration potential. Blocking the EGFR or the effector cytokines IFN-γ and TNF could inhibit tissue remodeling. This regenerative program enhanced tumor spheroid and stem cell-mediated organoid growth. Using single-cell gene expression analysis, we identified an AREG+, tissue-resident CD8 T cell population in skin and adipose tissue from patients undergoing abdominal wall or abdominoplasty surgery. These tissue-resident CD8 T cells showed a strong TCR clonal relation to blood PD1+TIGIT+ CD8 T cells with tissue remodeling abilities. These findings may help to understand the complex CD8 biology in tumors and could become relevant for the design of therapeutic T cell products., (© 2024 Delacher et al.)

Published
2024
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18. Analysis of organoid and immune cell co-cultures by machine learning-empowered image cytometry.

Author

Stüve P, Nerb B, Harrer S, Wuttke M, Feuerer M, Junger H, Eggenhofer E, Lungu B, Laslau S, and Ritter U

Abstract

Competing Interests: BL and SL were employed by TissueGnostics GmbH. UR acts as a scientific consultant for the company TissueGnostics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Published
2024
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19. Engineered Treg cells as putative therapeutics against inflammatory diseases and beyond.

Author

Bittner S, Hehlgans T, and Feuerer M

Subjects
Humans, Immune Tolerance, Immunotherapy, Adoptive, Inflammation therapy, T-Lymphocytes, Regulatory, Autoimmune Diseases therapy
Abstract

Regulatory T (Treg) cells ensure tolerance against self-antigens, limit excessive inflammation, and support tissue repair processes. Therefore, Treg cells are currently attractive candidates for the treatment of certain inflammatory diseases, autoimmune disorders, or transplant rejection. Early clinical trials have proved the safety and efficacy of certain Treg cell therapies in inflammatory diseases. We summarize recent advances in engineering Treg cells, including the concept of biosensors for inflammation. We assess Treg cell engineering possibilities for novel functional units, including Treg cell modifications influencing stability, migration, and tissue adaptation. Finally, we outline perspectives of engineered Treg cells going beyond inflammatory diseases by using custom-designed receptors and read-out systems, aiming to use Treg cells as in vivo diagnostic tools and drug delivery vehicles., Competing Interests: Declaration of interests S.B., T.H., and M.F. are inventors on a patent application (patent application no. EP22175091.2) based on the AIR-Treg technology., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Published
2023
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20. Biosensors for inflammation as a strategy to engineer regulatory T cells for cell therapy.

Author

Bittner S, Ruhland B, Hofmann V, Schmidleithner L, Schambeck K, Pant A, Stüve P, Delacher M, Echtenacher B, Edinger M, Hoffmann P, Rehli M, Gebhard C, Strieder N, Hehlgans T, and Feuerer M

Subjects
Animals, CD28 Antigens metabolism, Humans, Ligands, Lymphotoxin beta Receptor metabolism, Mice, Receptors, Antigen, T-Cell metabolism, Receptors, Tumor Necrosis Factor metabolism, Tumor Necrosis Factor-alpha, Biosensing Techniques, Cell Engineering, Cell- and Tissue-Based Therapy, Inflammation therapy, T-Lymphocytes, Regulatory transplantation
Abstract

Engineered regulatory T cell (Treg cell) therapy is a promising strategy to treat patients suffering from inflammatory diseases, autoimmunity, and transplant rejection. However, in many cases, disease-related antigens that can be targeted by Treg cells are not available. In this study, we introduce a class of synthetic biosensors, named artificial immune receptors (AIRs), for murine and human Treg cells. AIRs consist of three domains: (a) extracellular binding domain of a tumor necrosis factor (TNF)-receptor superfamily member, (b) intracellular costimulatory signaling domain of CD28, and (c) T cell receptor signaling domain of CD3-ζ chain. These AIR receptors equip Treg cells with an inflammation-sensing machinery and translate this environmental information into a CD3-ζ chain-dependent TCR-activation program. Different AIRs were generated, recognizing the inflammatory ligands of the TNF-receptor superfamily, including LIGHT, TNFα, and TNF-like ligand 1A (TL1A), leading to activation, differentiation, and proliferation of AIR-Treg cells. In a graft-versus-host disease model, Treg cells expressing lymphotoxin β receptor-AIR, which can be activated by the ligand LIGHT, protect significantly better than control Treg cells. Expression and signaling of the corresponding human AIR in human Treg cells prove that this concept can be translated. Engineering Treg cells that target inflammatory ligands leading to TCR signaling and activation might be used as a Treg cell-based therapy approach for a broad range of inflammation-driven diseases.

Published
2022
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22. LDHB Overexpression Can Partially Overcome T Cell Inhibition by Lactic Acid.

Author

Decking SM, Bruss C, Babl N, Bittner S, Klobuch S, Thomas S, Feuerer M, Hoffmann P, Dettmer K, Oefner PJ, Renner K, and Kreutz M

Subjects
Cell Line, Tumor, Cytokines metabolism, Glycolysis, Humans, L-Lactate Dehydrogenase genetics, L-Lactate Dehydrogenase metabolism, T-Lymphocytes metabolism, Lactate Dehydrogenases metabolism, Lactic Acid metabolism, Neoplasms metabolism
Abstract

Accelerated glycolysis leads to secretion and accumulation of lactate and protons in the tumor environment and determines the efficacy of adoptive T cell and checkpoint inhibition therapy. Here, we analyzed effects of lactic acid on different human CD4 T cell subsets and aimed to increase CD4 T cell resistance towards lactic acid. In all CD4 T cell subsets analyzed, lactic acid inhibited metabolic activity (glycolysis and respiration), cytokine secretion, and cell proliferation. Overexpression of the lactate-metabolizing isoenzyme LDHB increased cell respiration and mitigated lactic acid effects on intracellular cytokine production. Strikingly, LDHB-overexpressing cells preferentially migrated into HCT116 tumor spheroids and displayed higher expression of cytotoxic effector molecules. We conclude, that LDHB overexpression might be a promising strategy to increase the efficacy of adoptive T cell transfer therapy.

Published
2022
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23. Tfh cells induce intratumoral tertiary lymphoid structures.

Author

Schmidleithner L and Feuerer M

Subjects
Animals, Cell Differentiation, Humans, Mice, T Follicular Helper Cells, Matrix Attachment Region Binding Proteins, Neoplasms, Tertiary Lymphoid Structures pathology
Abstract

Tertiary lymphoid structures (TLS) are highly organized ectopic structures found in nonlymphoid organs under chronic inflammatory conditions, including cancer. A recent study by Chaurio et al. reports that repression of Satb1 in CD4 + T cells can lead to increased Tfh cell differentiation, driving intratumoral TLS formation, resulting in reduced tumor growth in mice., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Published
2022
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24. Interleukin-10 receptor signaling promotes the maintenance of a PD-1 int TCF-1 + CD8 + T cell population that sustains anti-tumor immunity.

Author

Hanna BS, Llaó-Cid L, Iskar M, Roessner PM, Klett LC, Wong JKL, Paul Y, Ioannou N, Öztürk S, Mack N, Kalter V, Colomer D, Campo E, Bloehdorn J, Stilgenbauer S, Dietrich S, Schmidt M, Gabriel R, Rippe K, Feuerer M, Ramsay AG, Lichter P, Zapatka M, and Seiffert M

Subjects
Animals, Cell Line, Tumor, Cells, Cultured, Cellular Microenvironment, Hepatocyte Nuclear Factor 1-alpha metabolism, Humans, Immunity, Mice, Mice, Inbred C57BL, NFATC Transcription Factors metabolism, Programmed Cell Death 1 Receptor metabolism, Receptors, Interleukin-10 genetics, STAT3 Transcription Factor genetics, STAT3 Transcription Factor metabolism, Signal Transduction, Transcription Factor AP-1 metabolism, CD8-Positive T-Lymphocytes immunology, Immunotherapy methods, Leukemia, Lymphocytic, Chronic, B-Cell immunology, Receptors, Interleukin-10 metabolism, T-Lymphocyte Subsets immunology
Abstract

T cell exhaustion limits anti-tumor immunity and responses to immunotherapy. Here, we explored the microenvironmental signals regulating T cell exhaustion using a model of chronic lymphocytic leukemia (CLL). Single-cell analyses identified a subset of PD-1 hi , functionally impaired CD8 + T cells that accumulated in secondary lymphoid organs during disease progression and a functionally competent PD-1 int subset. Frequencies of PD-1 int TCF-1 + CD8 + T cells decreased upon Il10rb or Stat3 deletion, leading to accumulation of PD-1 hi cells and accelerated tumor progression. Mechanistically, inhibition of IL-10R signaling altered chromatin accessibility and disrupted cooperativity between the transcription factors NFAT and AP-1, promoting a distinct NFAT-associated program. Low IL10 expression or loss of IL-10R-STAT3 signaling correlated with increased frequencies of exhausted CD8 + T cells and poor survival in CLL and in breast cancer patients. Thus, balance between PD-1 hi , exhausted CD8 + T cells and functional PD-1 int TCF-1 + CD8 + T cells is regulated by cell-intrinsic IL-10R signaling, with implications for immunotherapy., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Published
2021
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25. Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition).

Author

Cossarizza A, Chang HD, Radbruch A, Abrignani S, Addo R, Akdis M, Andrä I, Andreata F, Annunziato F, Arranz E, Bacher P, Bari S, Barnaba V, Barros-Martins J, Baumjohann D, Beccaria CG, Bernardo D, Boardman DA, Borger J, Böttcher C, Brockmann L, Burns M, Busch DH, Cameron G, Cammarata I, Cassotta A, Chang Y, Chirdo FG, Christakou E, Čičin-Šain L, Cook L, Corbett AJ, Cornelis R, Cosmi L, Davey MS, De Biasi S, De Simone G, Del Zotto G, Delacher M, Di Rosa F, Di Santo J, Diefenbach A, Dong J, Dörner T, Dress RJ, Dutertre CA, Eckle SBG, Eede P, Evrard M, Falk CS, Feuerer M, Fillatreau S, Fiz-Lopez A, Follo M, Foulds GA, Fröbel J, Gagliani N, Galletti G, Gangaev A, Garbi N, Garrote JA, Geginat J, Gherardin NA, Gibellini L, Ginhoux F, Godfrey DI, Gruarin P, Haftmann C, Hansmann L, Harpur CM, Hayday AC, Heine G, Hernández DC, Herrmann M, Hoelsken O, Huang Q, Huber S, Huber JE, Huehn J, Hundemer M, Hwang WYK, Iannacone M, Ivison SM, Jäck HM, Jani PK, Keller B, Kessler N, Ketelaars S, Knop L, Knopf J, Koay HF, Kobow K, Kriegsmann K, Kristyanto H, Krueger A, Kuehne JF, Kunze-Schumacher H, Kvistborg P, Kwok I, Latorre D, Lenz D, Levings MK, Lino AC, Liotta F, Long HM, Lugli E, MacDonald KN, Maggi L, Maini MK, Mair F, Manta C, Manz RA, Mashreghi MF, Mazzoni A, McCluskey J, Mei HE, Melchers F, Melzer S, Mielenz D, Monin L, Moretta L, Multhoff G, Muñoz LE, Muñoz-Ruiz M, Muscate F, Natalini A, Neumann K, Ng LG, Niedobitek A, Niemz J, Almeida LN, Notarbartolo S, Ostendorf L, Pallett LJ, Patel AA, Percin GI, Peruzzi G, Pinti M, Pockley AG, Pracht K, Prinz I, Pujol-Autonell I, Pulvirenti N, Quatrini L, Quinn KM, Radbruch H, Rhys H, Rodrigo MB, Romagnani C, Saggau C, Sakaguchi S, Sallusto F, Sanderink L, Sandrock I, Schauer C, Scheffold A, Scherer HU, Schiemann M, Schildberg FA, Schober K, Schoen J, Schuh W, Schüler T, Schulz AR, Schulz S, Schulze J, Simonetti S, Singh J, Sitnik KM, Stark R, Starossom S, Stehle C, Szelinski F, Tan L, Tarnok A, Tornack J, Tree TIM, van Beek JJP, van de Veen W, van Gisbergen K, Vasco C, Verheyden NA, von Borstel A, Ward-Hartstonge KA, Warnatz K, Waskow C, Wiedemann A, Wilharm A, Wing J, Wirz O, Wittner J, Yang JHM, and Yang J

Subjects
Animals, Chronic Disease, Humans, Mice, Practice Guidelines as Topic, Autoimmune Diseases immunology, Flow Cytometry, Infections immunology, Neoplasms immunology
Abstract

The third edition of Flow Cytometry Guidelines provides the key aspects to consider when performing flow cytometry experiments and includes comprehensive sections describing phenotypes and functional assays of all major human and murine immune cell subsets. Notably, the Guidelines contain helpful tables highlighting phenotypes and key differences between human and murine cells. Another useful feature of this edition is the flow cytometry analysis of clinical samples with examples of flow cytometry applications in the context of autoimmune diseases, cancers as well as acute and chronic infectious diseases. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid. All sections are written and peer-reviewed by leading flow cytometry experts and immunologists, making this edition an essential and state-of-the-art handbook for basic and clinical researchers., (© 2021 Wiley-VCH GmbH.)

Published
2021
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26. Single-cell chromatin accessibility landscape identifies tissue repair program in human regulatory T cells.

Author

Delacher M, Simon M, Sanderink L, Hotz-Wagenblatt A, Wuttke M, Schambeck K, Schmidleithner L, Bittner S, Pant A, Ritter U, Hehlgans T, Riegel D, Schneider V, Groeber-Becker FK, Eigenberger A, Gebhard C, Strieder N, Fischer A, Rehli M, Hoffmann P, Edinger M, Strowig T, Huehn J, Schmidl C, Werner JM, Prantl L, Brors B, Imbusch CD, and Feuerer M

Subjects
Adult, Animals, Basic-Leucine Zipper Transcription Factors immunology, Cell Differentiation immunology, Cell Line, Female, Gene Expression Profiling methods, Gene Expression Regulation immunology, HaCaT Cells, Humans, Male, Mice, Mice, Inbred C57BL, Middle Aged, Receptors, CCR8 immunology, T Follicular Helper Cells immunology, Chromatin immunology, T-Lymphocytes, Regulatory immunology, Wound Healing immunology
Abstract

Murine regulatory T (Treg) cells in tissues promote tissue homeostasis and regeneration. We sought to identify features that characterize human Treg cells with these functions in healthy tissues. Single-cell chromatin accessibility profiles of murine and human tissue Treg cells defined a conserved, microbiota-independent tissue-repair Treg signature with a prevailing footprint of the transcription factor BATF. This signature, combined with gene expression profiling and TCR fate mapping, identified a population of tissue-like Treg cells in human peripheral blood that expressed BATF, chemokine receptor CCR8 and HLA-DR. Human BATF + CCR8 + Treg cells from normal skin and adipose tissue shared features with nonlymphoid T follicular helper-like (Tfh-like) cells, and induction of a Tfh-like differentiation program in naive human Treg cells partially recapitulated tissue Treg regenerative characteristics, including wound healing potential. Human BATF + CCR8 + Treg cells from healthy tissue share features with tumor-resident Treg cells, highlighting the importance of understanding the context-specific functions of these cells., Competing Interests: Declaration of interest The authors declare no competing financial interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2021
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27. Inflammatory Response Mechanisms of the Dentine-Pulp Complex and the Periapical Tissues.

Author

Galler KM, Weber M, Korkmaz Y, Widbiller M, and Feuerer M

Subjects
Animals, Antigens, Neoplasm immunology, Carcinogenesis immunology, Carcinoma, Squamous Cell etiology, Carcinoma, Squamous Cell immunology, Carcinoma, Squamous Cell physiopathology, Chemokines metabolism, Complement System Proteins metabolism, Dental Caries physiopathology, Dental Pulp microbiology, Dentin blood supply, Dentin innervation, Dentin metabolism, Fibroblasts immunology, Fibroblasts metabolism, Humans, Intracellular Signaling Peptides and Proteins physiology, Mesenchymal Stem Cells physiology, Mouth Neoplasms etiology, Mouth Neoplasms immunology, Mouth Neoplasms physiopathology, Nerve Net physiology, Neuropeptides metabolism, Nitric Oxide physiology, Odontoblasts physiology, Periapical Granuloma etiology, Periapical Granuloma pathology, Periapical Tissue microbiology, Radicular Cyst etiology, Radicular Cyst physiopathology, Dental Pulp pathology, Periapical Periodontitis pathology, Periapical Tissue pathology, Pulpitis pathology
Abstract

The macroscopic and microscopic anatomy of the oral cavity is complex and unique in the human body. Soft-tissue structures are in close interaction with mineralized bone, but also dentine, cementum and enamel of our teeth. These are exposed to intense mechanical and chemical stress as well as to dense microbiologic colonization. Teeth are susceptible to damage, most commonly to caries, where microorganisms from the oral cavity degrade the mineralized tissues of enamel and dentine and invade the soft connective tissue at the core, the dental pulp. However, the pulp is well-equipped to sense and fend off bacteria and their products and mounts various and intricate defense mechanisms. The front rank is formed by a layer of odontoblasts, which line the pulp chamber towards the dentine. These highly specialized cells not only form mineralized tissue but exert important functions as barrier cells. They recognize pathogens early in the process, secrete antibacterial compounds and neutralize bacterial toxins, initiate the immune response and alert other key players of the host defense. As bacteria get closer to the pulp, additional cell types of the pulp, including fibroblasts, stem and immune cells, but also vascular and neuronal networks, contribute with a variety of distinct defense mechanisms, and inflammatory response mechanisms are critical for tissue homeostasis. Still, without therapeutic intervention, a deep carious lesion may lead to tissue necrosis, which allows bacteria to populate the root canal system and invade the periradicular bone via the apical foramen at the root tip. The periodontal tissues and alveolar bone react to the insult with an inflammatory response, most commonly by the formation of an apical granuloma. Healing can occur after pathogen removal, which is achieved by disinfection and obturation of the pulp space by root canal treatment. This review highlights the various mechanisms of pathogen recognition and defense of dental pulp cells and periradicular tissues, explains the different cell types involved in the immune response and discusses the mechanisms of healing and repair, pointing out the close links between inflammation and regeneration as well as between inflammation and potential malignant transformation.

Published
2021
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28. Recirculating IL-1R2 + Tregs fine-tune intrathymic Treg development under inflammatory conditions.

Author

Nikolouli E, Elfaki Y, Herppich S, Schelmbauer C, Delacher M, Falk C, Mufazalov IA, Waisman A, Feuerer M, and Huehn J

Subjects
Animals, Cytokines metabolism, Homeodomain Proteins physiology, Inflammation metabolism, Inflammation pathology, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Spleen cytology, Spleen immunology, Spleen metabolism, T-Lymphocytes, Regulatory immunology, T-Lymphocytes, Regulatory metabolism, Thymocytes immunology, Thymocytes metabolism, Cell Differentiation, Forkhead Transcription Factors physiology, Inflammation immunology, Receptors, Interleukin-1 Type II metabolism, T-Lymphocytes, Regulatory cytology, Thymocytes cytology
Abstract

The vast majority of Foxp3 + regulatory T cells (Tregs) are generated in the thymus, and several factors, such as cytokines and unique thymic antigen-presenting cells, are known to contribute to the development of these thymus-derived Tregs (tTregs). Here, we report the existence of a specific subset of Foxp3 + Tregs within the thymus that is characterized by the expression of IL-1R2, which is a decoy receptor for the inflammatory cytokine IL-1. Detailed flow cytometric analysis of the thymocytes from Foxp3 hCD2 xRAG1 GFP reporter mice revealed that the IL-1R2 + Tregs are mainly RAG1 GFP- and CCR6 + CCR7 - , demonstrating that these Tregs are recirculating cells entering the thymus from the periphery and that they have an activated phenotype. In the spleen, the majority of IL-1R2 + Tregs express neuropilin-1 (Nrp-1) and Helios, suggesting a thymic origin for these Tregs. Interestingly, among all tissues studied, the highest frequency of IL-1R2 + Tregs was observed in the thymus, indicating preferential recruitment of this Treg subset by the thymus. Using fetal thymic organ cultures (FTOCs), we demonstrated that increased concentrations of exogenous IL-1β blocked intrathymic Treg development, resulting in a decreased frequency of CD25 + Foxp3 + tTregs and an accumulation of CD25 + Foxp3 - Treg precursors. Interestingly, the addition of IL-1R2 + Tregs, but not IL-1R2 - Tregs, to reaggregated thymic organ cultures (RTOCs) abrogated the IL-1β-mediated blockade, demonstrating that these recirculating IL-1R2 + Tregs can quench IL-1 signaling in the thymus and thereby maintain thymic Treg development even under inflammatory conditions.

Published
2021
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29. Quantitative Proteomics Identifies TCF1 as a Negative Regulator of Foxp3 Expression in Conventional T Cells.

Author

Delacher M, Barra MM, Herzig Y, Eichelbaum K, Rafiee MR, Richards DM, Träger U, Hofer AC, Kazakov A, Braband KL, Gonzalez M, Wöhrl L, Schambeck K, Imbusch CD, Abramson J, Krijgsveld J, and Feuerer M

Abstract

Regulatory T cells are important regulators of the immune system and have versatile functions for the homeostasis and repair of tissues. They express the forkhead box transcription factor Foxp3 as a lineage-defining protein. Negative regulators of Foxp3 expression are not well understood. Here, we generated double-stranded DNA probes complementary to the Foxp3 promoter sequence and performed a pull-down with nuclear protein in vitro, followed by elution of bound proteins and quantitative mass spectrometry. Of the Foxp3-promoter-binding transcription factors identified with this approach, one was T cell factor 1 (TCF1). Using viral over-expression, we identified TCF1 as a repressor of Foxp3 expression. In TCF1-deficient animals, increased levels of Foxp3 intermediate CD25 negative T cells were identified. CRISPR-Cas9 knockout studies in primary human and mouse conventional CD4 T (T conv ) cells revealed that TCF1 protects T conv cells from inadvertent Foxp3 expression. Our data implicate a role of TCF1 in suppressing Foxp3 expression in activated T cells., Competing Interests: Declaration of Interests The authors declare no competing financial interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2020
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30. International Regensburg Center for Interventional Immunology (RCI) symposium on "Synthetic immunology and environment-adapted redirection of T cells", 17-18 July, 2019, Regensburg, Germany.

Author

Beckhove P, Edinger M, Feuerer M, Gattinoni L, and Abken H

Subjects
Autoimmune Diseases immunology, Congresses as Topic, Germany, Humans, Neoplasms immunology, Autoimmune Diseases therapy, Immunotherapy, Adoptive methods, Neoplasms therapy, Receptors, Antigen, T-Cell immunology, T-Lymphocytes, Regulatory immunology
Published
2020
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31. Precursors for Nonlymphoid-Tissue Treg Cells Reside in Secondary Lymphoid Organs and Are Programmed by the Transcription Factor BATF.

Author

Delacher M, Imbusch CD, Hotz-Wagenblatt A, Mallm JP, Bauer K, Simon M, Riegel D, Rendeiro AF, Bittner S, Sanderink L, Pant A, Schmidleithner L, Braband KL, Echtenachter B, Fischer A, Giunchiglia V, Hoffmann P, Edinger M, Bock C, Rehli M, Brors B, Schmidl C, and Feuerer M

Subjects
Adoptive Transfer, Animals, Basic-Leucine Zipper Transcription Factors deficiency, Basic-Leucine Zipper Transcription Factors genetics, Cell Differentiation genetics, Chromatin metabolism, GATA3 Transcription Factor genetics, GATA3 Transcription Factor metabolism, Gene Expression Profiling, Gene Expression Regulation immunology, Interleukin-1 Receptor-Like 1 Protein metabolism, Lectins, C-Type genetics, Lectins, C-Type metabolism, Mice, Organ Specificity immunology, Receptors, Immunologic genetics, Receptors, Immunologic metabolism, T-Lymphocytes, Regulatory metabolism, Basic-Leucine Zipper Transcription Factors metabolism, Lymph Nodes immunology, Spleen immunology, T-Lymphocytes, Regulatory cytology
Abstract

Specialized regulatory T (Treg) cells accumulate and perform homeostatic and regenerative functions in nonlymphoid tissues. Whether common precursors for nonlymphoid-tissue Treg cells exist and how they differentiate remain elusive. Using transcription factor nuclear factor, interleukin 3 regulated (Nfil3) reporter mice and single-cell RNA-sequencing (scRNA-seq), we identified two precursor stages of interleukin 33 (IL-33) receptor ST2-expressing nonlymphoid tissue Treg cells, which resided in the spleen and lymph nodes. Global chromatin profiling of nonlymphoid tissue Treg cells and the two precursor stages revealed a stepwise acquisition of chromatin accessibility and reprogramming toward the nonlymphoid-tissue Treg cell phenotype. Mechanistically, we identified and validated the transcription factor Batf as the driver of the molecular tissue program in the precursors. Understanding this tissue development program will help to harness regenerative properties of tissue Treg cells for therapy., Competing Interests: Declaration of Interests The authors declare no competing financial interests., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Published
2020
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32. Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition).

Author

Cossarizza A, Chang HD, Radbruch A, Acs A, Adam D, Adam-Klages S, Agace WW, Aghaeepour N, Akdis M, Allez M, Almeida LN, Alvisi G, Anderson G, Andrä I, Annunziato F, Anselmo A, Bacher P, Baldari CT, Bari S, Barnaba V, Barros-Martins J, Battistini L, Bauer W, Baumgart S, Baumgarth N, Baumjohann D, Baying B, Bebawy M, Becher B, Beisker W, Benes V, Beyaert R, Blanco A, Boardman DA, Bogdan C, Borger JG, Borsellino G, Boulais PE, Bradford JA, Brenner D, Brinkman RR, Brooks AES, Busch DH, Büscher M, Bushnell TP, Calzetti F, Cameron G, Cammarata I, Cao X, Cardell SL, Casola S, Cassatella MA, Cavani A, Celada A, Chatenoud L, Chattopadhyay PK, Chow S, Christakou E, Čičin-Šain L, Clerici M, Colombo FS, Cook L, Cooke A, Cooper AM, Corbett AJ, Cosma A, Cosmi L, Coulie PG, Cumano A, Cvetkovic L, Dang VD, Dang-Heine C, Davey MS, Davies D, De Biasi S, Del Zotto G, Dela Cruz GV, Delacher M, Della Bella S, Dellabona P, Deniz G, Dessing M, Di Santo JP, Diefenbach A, Dieli F, Dolf A, Dörner T, Dress RJ, Dudziak D, Dustin M, Dutertre CA, Ebner F, Eckle SBG, Edinger M, Eede P, Ehrhardt GRA, Eich M, Engel P, Engelhardt B, Erdei A, Esser C, Everts B, Evrard M, Falk CS, Fehniger TA, Felipo-Benavent M, Ferry H, Feuerer M, Filby A, Filkor K, Fillatreau S, Follo M, Förster I, Foster J, Foulds GA, Frehse B, Frenette PS, Frischbutter S, Fritzsche W, Galbraith DW, Gangaev A, Garbi N, Gaudilliere B, Gazzinelli RT, Geginat J, Gerner W, Gherardin NA, Ghoreschi K, Gibellini L, Ginhoux F, Goda K, Godfrey DI, Goettlinger C, González-Navajas JM, Goodyear CS, Gori A, Grogan JL, Grummitt D, Grützkau A, Haftmann C, Hahn J, Hammad H, Hämmerling G, Hansmann L, Hansson G, Harpur CM, Hartmann S, Hauser A, Hauser AE, Haviland DL, Hedley D, Hernández DC, Herrera G, Herrmann M, Hess C, Höfer T, Hoffmann P, Hogquist K, Holland T, Höllt T, Holmdahl R, Hombrink P, Houston JP, Hoyer BF, Huang B, Huang FP, Huber JE, Huehn J, Hundemer M, Hunter CA, Hwang WYK, Iannone A, Ingelfinger F, Ivison SM, Jäck HM, Jani PK, Jávega B, Jonjic S, Kaiser T, Kalina T, Kamradt T, Kaufmann SHE, Keller B, Ketelaars SLC, Khalilnezhad A, Khan S, Kisielow J, Klenerman P, Knopf J, Koay HF, Kobow K, Kolls JK, Kong WT, Kopf M, Korn T, Kriegsmann K, Kristyanto H, Kroneis T, Krueger A, Kühne J, Kukat C, Kunkel D, Kunze-Schumacher H, Kurosaki T, Kurts C, Kvistborg P, Kwok I, Landry J, Lantz O, Lanuti P, LaRosa F, Lehuen A, LeibundGut-Landmann S, Leipold MD, Leung LYT, Levings MK, Lino AC, Liotta F, Litwin V, Liu Y, Ljunggren HG, Lohoff M, Lombardi G, Lopez L, López-Botet M, Lovett-Racke AE, Lubberts E, Luche H, Ludewig B, Lugli E, Lunemann S, Maecker HT, Maggi L, Maguire O, Mair F, Mair KH, Mantovani A, Manz RA, Marshall AJ, Martínez-Romero A, Martrus G, Marventano I, Maslinski W, Matarese G, Mattioli AV, Maueröder C, Mazzoni A, McCluskey J, McGrath M, McGuire HM, McInnes IB, Mei HE, Melchers F, Melzer S, Mielenz D, Miller SD, Mills KHG, Minderman H, Mjösberg J, Moore J, Moran B, Moretta L, Mosmann TR, Müller S, Multhoff G, Muñoz LE, Münz C, Nakayama T, Nasi M, Neumann K, Ng LG, Niedobitek A, Nourshargh S, Núñez G, O'Connor JE, Ochel A, Oja A, Ordonez D, Orfao A, Orlowski-Oliver E, Ouyang W, Oxenius A, Palankar R, Panse I, Pattanapanyasat K, Paulsen M, Pavlinic D, Penter L, Peterson P, Peth C, Petriz J, Piancone F, Pickl WF, Piconese S, Pinti M, Pockley AG, Podolska MJ, Poon Z, Pracht K, Prinz I, Pucillo CEM, Quataert SA, Quatrini L, Quinn KM, Radbruch H, Radstake TRDJ, Rahmig S, Rahn HP, Rajwa B, Ravichandran G, Raz Y, Rebhahn JA, Recktenwald D, Reimer D, Reis e Sousa C, Remmerswaal EBM, Richter L, Rico LG, Riddell A, Rieger AM, Robinson JP, Romagnani C, Rubartelli A, Ruland J, Saalmüller A, Saeys Y, Saito T, Sakaguchi S, Sala-de-Oyanguren F, Samstag Y, Sanderson S, Sandrock I, Santoni A, Sanz RB, Saresella M, Sautes-Fridman C, Sawitzki B, Schadt L, Scheffold A, Scherer HU, Schiemann M, Schildberg FA, Schimisky E, Schlitzer A, Schlosser J, Schmid S, Schmitt S, Schober K, Schraivogel D, Schuh W, Schüler T, Schulte R, Schulz AR, Schulz SR, Scottá C, Scott-Algara D, Sester DP, Shankey TV, Silva-Santos B, Simon AK, Sitnik KM, Sozzani S, Speiser DE, Spidlen J, Stahlberg A, Stall AM, Stanley N, Stark R, Stehle C, Steinmetz T, Stockinger H, Takahama Y, Takeda K, Tan L, Tárnok A, Tiegs G, Toldi G, Tornack J, Traggiai E, Trebak M, Tree TIM, Trotter J, Trowsdale J, Tsoumakidou M, Ulrich H, Urbanczyk S, van de Veen W, van den Broek M, van der Pol E, Van Gassen S, Van Isterdael G, van Lier RAW, Veldhoen M, Vento-Asturias S, Vieira P, Voehringer D, Volk HD, von Borstel A, von Volkmann K, Waisman A, Walker RV, Wallace PK, Wang SA, Wang XM, Ward MD, Ward-Hartstonge KA, Warnatz K, Warnes G, Warth S, Waskow C, Watson JV, Watzl C, Wegener L, Weisenburger T, Wiedemann A, Wienands J, Wilharm A, Wilkinson RJ, Willimsky G, Wing JB, Winkelmann R, Winkler TH, Wirz OF, Wong A, Wurst P, Yang JHM, Yang J, Yazdanbakhsh M, Yu L, Yue A, Zhang H, Zhao Y, Ziegler SM, Zielinski C, Zimmermann J, and Zychlinsky A

Subjects
Consensus, Humans, Phenotype, Allergy and Immunology standards, Cell Separation methods, Cell Separation standards, Flow Cytometry methods, Flow Cytometry standards
Abstract

These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Published
2019
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33. A transplantable tumor model allowing investigation of NY-BR-1-specific T cell responses in HLA-DRB1*0401 transgenic mice.

Author

Das K, Eisel D, Vormehr M, Müller-Decker K, Hommertgen A, Jäger D, Zörnig I, Feuerer M, Kopp-Schneider A, Osen W, and Eichmüller SB

Subjects
Animals, Antigens, Neoplasm genetics, Biomarkers, Cell Line, Tumor, Disease Models, Animal, HLA-DRB1 Chains immunology, Heterografts, Humans, Immunization, Immunophenotyping, Leukocytes immunology, Leukocytes metabolism, Mice, Mice, Transgenic, T-Lymphocyte Subsets immunology, T-Lymphocyte Subsets metabolism, Antigens, Neoplasm immunology, Epitopes, T-Lymphocyte immunology, HLA-DRB1 Chains genetics, Neoplasms etiology, Neoplasms pathology, T-Lymphocytes immunology, T-Lymphocytes metabolism
Abstract

Background: NY-BR-1 has been described as a breast cancer associated differentiation antigen with intrinsic immunogenicity giving rise to endogenous T and B cell responses. The current study presents the first murine tumor model allowing functional investigation of NY-BR-1-specific immune responses in vivo., Methods: A NY-BR-1 expressing tumor model was established in DR4tg mice based on heterotopic transplantation of stable transfectant clones derived from the murine H2 compatible breast cancer cell line EO771. Composition and phenotype of tumor infiltrating immune cells were analyzed by qPCR and FACS. MHC I binding affinity of candidate CTL epitopes predicted in silico was determined by FACS using the mutant cell line RMA-S. Frequencies of NY-BR-1 specific CTLs among splenocytes of immunized mice were quantified by FACS with an epitope loaded D b -dextramer. Functional CTL activity was determined by IFNγ catch or IFNγ ELISpot assays and statistical analysis was done applying the Mann Whitney test. Tumor protection experiments were performed by immunization of DR4tg mice with replication deficient recombinant adenovirus followed by s.c. challenge with NY-BR-1 expressing breast cancer cells., Results: Our results show spontaneous accumulation of CD8 + T cells and F4/80 + myeloid cells preferentially in NY-BR-1 expressing tumors. Upon NY-BR-1-specific immunization experiments combined with in silico prediction and in vitro binding assays, the first NY-BR-1-specific H2-D b -restricted T cell epitope could be identified. Consequently, flow cytometric analysis with fluorochrome conjugated multimers showed enhanced frequencies of CD8 + T cells specific for the newly identified epitope in spleens of immunized mice. Moreover, immunization with Ad.NY-BR-1 resulted in partial protection against outgrowth of NY-BR-1 expressing tumors and promoted intratumoral accumulation of macrophages., Conclusion: This study introduces the first H2-D b -resctricted CD8 + T cell epitope-specific for the human breast cancer associated tumor antigen NY-BR-1. Our novel, partially humanized tumor model enables investigation of the interplay between HLA-DR4-restricted T cell responses and CTLs within their joint attack of NY-BR-1 expressing tumors.

Published
2019
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34. Rbpj expression in regulatory T cells is critical for restraining T H 2 responses.

Author

Delacher M, Schmidl C, Herzig Y, Breloer M, Hartmann W, Brunk F, Kägebein D, Träger U, Hofer AC, Bittner S, Weichenhan D, Imbusch CD, Hotz-Wagenblatt A, Hielscher T, Breiling A, Federico G, Gröne HJ, Schmid RM, Rehli M, Abramson J, and Feuerer M

Subjects
Animals, Cell Differentiation immunology, Disease Models, Animal, Female, GATA3 Transcription Factor metabolism, Gene Expression Profiling, Gene Expression Regulation immunology, Germinal Center immunology, Humans, Immunoglobulin J Recombination Signal Sequence-Binding Protein genetics, Immunoglobulin J Recombination Signal Sequence-Binding Protein immunology, Lymphocyte Activation, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Strongyloides ratti immunology, Strongyloides ratti pathogenicity, Strongyloidiasis parasitology, T-Lymphocytes, Regulatory metabolism, Transcriptome immunology, Immunity, Cellular, Immunoglobulin J Recombination Signal Sequence-Binding Protein metabolism, Strongyloidiasis immunology, T-Lymphocytes, Regulatory immunology, Th2 Cells immunology
Abstract

The transcriptional regulator Rbpj is involved in T-helper (T H ) subset polarization, but its function in T reg cells remains unclear. Here we show that T reg -specific Rbpj deletion leads to splenomegaly and lymphadenopathy despite increased numbers of T reg cells with a polyclonal TCR repertoire. A specific defect of Rbpj-deficient T reg cells in controlling T H 2 polarization and B cell responses is observed, leading to the spontaneous formation of germinal centers and a T H 2-associated immunoglobulin class switch. The observed phenotype is environment-dependent and can be induced by infection with parasitic nematodes. Rbpj-deficient T reg cells adopt open chromatin landscapes and gene expression profiles reminiscent of tissue-derived T H 2-polarized T reg cells, with a prevailing signature of the transcription factor Gata-3. Taken together, our study suggests that T reg cells require Rbpj to specifically restrain T H 2 responses, including their own excessive T H 2-like differentiation potential.

Published
2019
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35. Epigenetic mechanisms regulating T-cell responses.

Author

Schmidl C, Delacher M, Huehn J, and Feuerer M

Subjects
Animals, Cell Differentiation, Humans, Thymus Gland cytology, Epigenesis, Genetic, T-Lymphocytes cytology
Abstract

During the last decade, advances in sequencing technologies allowed production of a wealth of information on epigenetic modifications in T cells. Epigenome maps, in combination with mechanistic studies, have demonstrated that T cells undergo extensive epigenome remodeling in response to signals, which has a strong effect on phenotypic stability and function of lymphocytes. In this review we focus on DNA methylation, histone modifications, and chromatin structure as important epigenetic mechanisms involved in controlling T-cell responses. In particular, we discuss epigenetic processes in light of the development, activation, and differentiation of CD4 + T helper (T H ), regulatory T, and CD8 + T cells. As central aspects of the adaptive immune system, we review mechanisms that ensure molecular memory, stability, plasticity, and exhaustion of T cells. We further discuss the effect of the tissue environment on imprinting T-cell epigenomes with potential implications for immunotherapy., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Published
2018
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37. Genome-wide DNA-methylation landscape defines specialization of regulatory T cells in tissues.

Author

Delacher M, Imbusch CD, Weichenhan D, Breiling A, Hotz-Wagenblatt A, Träger U, Hofer AC, Kägebein D, Wang Q, Frauhammer F, Mallm JP, Bauer K, Herrmann C, Lang PA, Brors B, Plass C, and Feuerer M

Subjects
Animals, Biomarkers, Cluster Analysis, Computational Biology methods, CpG Islands, Epigenesis, Genetic, Gene Expression Profiling, Gene Expression Regulation, Gene Ontology, High-Throughput Nucleotide Sequencing, Immunophenotyping, Mice, Mice, Transgenic, Molecular Sequence Annotation, Organ Specificity genetics, Organ Specificity immunology, Promoter Regions, Genetic, Th2 Cells metabolism, Transcription Initiation Site, Transcriptome, DNA Methylation, Genome-Wide Association Study, T-Lymphocytes, Regulatory metabolism
Abstract

Regulatory T cells (T reg cells) perform two distinct functions: they maintain self-tolerance, and they support organ homeostasis by differentiating into specialized tissue T reg cells. We found that epigenetic modifications defined the molecular characteristics of tissue T reg cells. Tagmentation-based whole-genome bisulfite sequencing revealed more than 11,000 regions that were methylated differentially in pairwise comparisons of tissue T reg cell populations and lymphoid T cells. Similarities in the epigenetic landscape led to the identification of a common tissue T reg cell population that was present in many organs and was characterized by gain and loss of DNA methylation that included many gene sites associated with the T H 2 subset of helper T cells, such as the gene encoding cytokine IL-33 receptor ST2, as well as the production of tissue-regenerative factors. Furthermore, the ST2-expressing population was dependent on the transcriptional regulator BATF and could be expanded by IL-33. Thus, tissue T reg cells integrate multiple waves of epigenetic reprogramming that define their tissue-restricted specialization.

Published
2017
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38. Transcriptional programs that control expression of the autoimmune regulator gene Aire.

Author

Herzig Y, Nevo S, Bornstein C, Brezis MR, Ben-Hur S, Shkedy A, Eisenberg-Bord M, Levi B, Delacher M, Goldfarb Y, David E, Weinberger L, Viukov S, Ben-Dor S, Giraud M, Hanna JH, Breiling A, Lyko F, Amit I, Feuerer M, and Abramson J

Subjects
Animals, Antigen Presentation genetics, Autoantigens metabolism, CCCTC-Binding Factor, Cell Differentiation, Cells, Cultured, Clonal Selection, Antigen-Mediated, DNA Methylation, Gene Expression Regulation, Interferon Regulatory Factors genetics, Interferon Regulatory Factors metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Organ Specificity genetics, Repressor Proteins genetics, Repressor Proteins metabolism, T-Box Domain Proteins genetics, T-Box Domain Proteins metabolism, Thymus Gland cytology, Transcription Factors genetics, AIRE Protein, Epithelial Cells immunology, Gene Regulatory Networks, T-Lymphocytes physiology, Thymus Gland immunology, Transcription Factors metabolism
Abstract

Aire is a transcriptional regulator that induces promiscuous expression of thousands of genes encoding tissue-restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs). While the target genes of Aire are well characterized, the transcriptional programs that regulate its own expression have remained elusive. Here we comprehensively analyzed both cis-acting and trans-acting regulatory mechanisms and found that the Aire locus was insulated by the global chromatin organizer CTCF and was hypermethylated in cells and tissues that did not express Aire. In mTECs, however, Aire expression was facilitated by concurrent eviction of CTCF, specific demethylation of exon 2 and the proximal promoter, and the coordinated action of several transcription activators, including Irf4, Irf8, Tbx21, Tcf7 and Ctcfl, which acted on mTEC-specific accessible regions in the Aire locus.

Published
2017
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39. The stress kinase GCN2 does not mediate suppression of antitumor T cell responses by tryptophan catabolism in experimental melanomas.

Author

Sonner JK, Deumelandt K, Ott M, Thomé CM, Rauschenbach KJ, Schulz S, Munteanu B, Mohapatra S, Adam I, Hofer AC, Feuerer M, Opitz CA, Hopf C, Wick W, and Platten M

Abstract

Tryptophan metabolism is a key process that shapes the immunosuppressive tumor microenvironment. The two rate-limiting enzymes that mediate tryptophan depletion, indoleamine-2,3-dioxygenase (IDO) and tryptophan-2,3-dioxygenase (TDO), have moved into the focus of research and inhibitors targeting IDO and TDO have entered clinical trials. Local tryptophan depletion is generally viewed as the crucial immunosuppressive mechanism. In T cells, the kinase general control non-derepressible 2 (GCN2) has been identified as a molecular sensor of tryptophan deprivation. GCN2 activation by tryptophan depletion induces apoptosis and mitigates T cell proliferation. Here, we investigated whether GCN2 attenuates tumor rejection in experimental B16 melanoma using T cell-specific Gcn2 knockout mice. Our data demonstrate that GCN2 in T cells did not affect immunity to B16 tumors even when animals were treated with antibodies targeting cytotoxic T lymphocyte antigen-4 (CTLA4). GCN2-deficient gp100 TCR-transgenic T cells were equally effective as wild-type pmel T cells against gp100-expressing B16 melanomas after adoptive transfer and gp100 peptide vaccination. Even augmentation of tumoral tryptophan metabolism in B16 tumors by lentiviral overexpression of Tdo did not differentially affect GCN2-proficient vs. GCN2-deficient T cells in vivo . Importantly, GCN2 target genes were not upregulated in tumor-infiltrating T cells. MALDI-TOF MS imaging of B16 melanomas demonstrated maintenance of intratumoral tryptophan levels despite high tryptophan turnover, which prohibits a drop in tryptophan sufficient to activate GCN2 in tumor-infiltrating T cells. In conclusion, our results do not suggest that suppression of antitumor immune responses by tryptophan metabolism is driven by local tryptophan depletion and subsequent GCN2-mediated T cell anergy.

Published
2016
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40. Epidermal Nbn deletion causes premature hair loss and a phenotype resembling psoriasiform dermatitis.

Author

Seidel P, Remus M, Delacher M, Grigaravicius P, Reuss DE, Frappart L, von Deimling A, Feuerer M, Abdollahi A, and Frappart PO

Subjects
Alopecia pathology, Animals, DNA-Binding Proteins, Dermatitis metabolism, Epidermis metabolism, Mice, Mice, Knockout, Phenotype, Psoriasis metabolism, Alopecia etiology, Cell Cycle Proteins physiology, Dermatitis pathology, Epidermis pathology, Nuclear Proteins physiology, Psoriasis pathology, Tumor Suppressor Protein p53 physiology
Abstract

Nijmegen Breakage Syndrome is a disease caused by NBN mutations. Here, we report a novel function of Nbn in skin homeostasis. We found that Nbn deficiency in hair follicle (HF) progenitors promoted increased DNA damage signaling, stimulating p16Ink4a up-regulation, Trp53 stabilization and cytokines secretion leading to HF-growth arrest and hair loss. At later stages, the basal keratinocytes layer exhibited also enhanced DNA damage response but in contrast to the one in HF progenitor was not associated with pro-inflammatory cytokines expression, but rather increased proliferation, lack of differentiation and immune response resembling psoriasiform dermatitis. Simultaneous Nbn and Trp53 inactivation significantly exacerbated this phenotype, due to the lack of inhibition of pro-inflammatory cytokines secretion by Trp53. Altogether, we demonstrated novel functions of Nbn in HF maintenance and prevention of skin inflammation and we provide a mechanistic explanation that links cell intrinsic DNA maintenance with large scale morphological tissue alterations., Competing Interests: The authors state no conflict of interest.

Published
2016
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41. Re-examining the Nature and Function of Self-Reactive T cells.

Author

Richards DM, Kyewski B, and Feuerer M

Subjects
Animals, Autoantigens immunology, Humans, Peripheral Tolerance, Receptors, Antigen, T-Cell metabolism, Autoimmune Diseases immunology, T-Lymphocyte Subsets physiology, T-Lymphocytes physiology
Abstract

Recent studies have leveraged MHC tetramer and TCR sequencing approaches towards a more precise characterization of the peripheral T cell repertoire, providing important insight into both the contribution of self-reactive T cells to the overall repertoire and their function. The peripheral T cell repertoire of healthy individuals contains a high frequency of diverse, self-reactive T cells. Furthermore, self-reactive T cells can perform essential beneficial physiological functions. We review these recent findings here, and discuss their implications to the current understanding of peripheral tolerance and the role of self-reactive T cells in autoimmune disease. We outline gaps in understanding, and argue that an important step forward is to revise the definition of self-reactive T cells to incorporate new concepts regarding the nature and physiological functions of different populations of T cells capable of recognizing self-antigens., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Published
2016
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42. Transcription Factor 7 Limits Regulatory T Cell Generation in the Thymus.

Author

Barra MM, Richards DM, Hansson J, Hofer AC, Delacher M, Hettinger J, Krijgsveld J, and Feuerer M

Subjects
Animals, Cell Lineage immunology, Cell Proliferation, Forkhead Transcription Factors metabolism, Gene Expression Profiling, Hematopoiesis genetics, Hepatocyte Nuclear Factor 1-alpha genetics, Mice, Mice, Inbred C57BL, Mice, Knockout, Proteome analysis, Signal Transduction immunology, T-Lymphocytes, Regulatory cytology, beta Catenin metabolism, Hematopoiesis immunology, Hepatocyte Nuclear Factor 1-alpha physiology, T-Lymphocytes, Regulatory immunology, Thymus Gland immunology
Abstract

Regulatory T cells (Tregs) differentiate in the thymus, but the mechanisms that control this process are not fully understood. We generated a comprehensive quantitative and differential proteome of murine Tregs and conventional T cells. We identified 5225 proteins, 164 of which were differentially expressed in Tregs. Together with the comparative analysis of proteome and gene expression data, we identified TCF7 as a promising candidate. Genetic elimination of transcription factor 7 (TCF7) led to increased fractions of Tregs in the thymus. Reduced levels of TCF7, found in the heterozygote, resulted in a greater potential for Treg precursors to differentiate into the Treg lineage. In contrast, activation of TCF7 through β-catenin had the opposite effect. TCF7 levels influenced the required TCR signaling strength of Treg precursors, and TCF7 deficiency broadened the repertoire and allowed lower TCR affinities to be recruited into the Treg lineage. FOXP3 was able to repress TCF7 protein expression. In summary, we propose a regulatory role for TCF7 in limiting access to the Treg lineage., (Copyright © 2015 by The American Association of Immunologists, Inc.)

Published
2015
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43. The Contained Self-Reactive Peripheral T Cell Repertoire: Size, Diversity, and Cellular Composition.

Author

Richards DM, Ruggiero E, Hofer AC, Sefrin JP, Schmidt M, von Kalle C, and Feuerer M

Subjects
Adoptive Transfer, Animals, CD4-Positive T-Lymphocytes metabolism, CD8-Positive T-Lymphocytes metabolism, Cell Line, Tumor, Cytokines immunology, Cytokines metabolism, Female, Flow Cytometry, Gene Expression Profiling, Male, Mice, Congenic, Mice, Inbred C57BL, Mice, Transgenic, Oligonucleotide Array Sequence Analysis, Precursor Cells, T-Lymphoid immunology, Precursor Cells, T-Lymphoid metabolism, Receptors, Antigen, T-Cell genetics, Receptors, Antigen, T-Cell metabolism, T-Lymphocytes, Regulatory immunology, T-Lymphocytes, Regulatory metabolism, CD4-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes immunology, Lymphocyte Activation immunology, Receptors, Antigen, T-Cell immunology
Abstract

Individual self-reactive T cells have been discovered in both humans and mice. It is difficult to assess the entire contained self-reactive peripheral T cell repertoire in healthy individuals because regulatory T cells (Tregs) can render these cells anergic and, therefore, functionally indistinguishable. We addressed this issue by removing regulatory T cells, thereby allowing us to characterize the exposed self-reactive T cells. This resulted in activation of approximately 4% of both CD4(+) and CD8(+) T cells. Activation and division of these cells was not a bystander product of Ag-independent signals but required TCR stimulation. Analysis of TCR sequences showed that these responding cells were polyclonal and encompassed a broad range of structural TCR diversity. Adoptive transfer of naive and effector/memory T cell populations showed that even the naive T cell pool contained self-reactive T cell precursors. In addition, transfer of mature thymocytes showed that this response was an intrinsic T cell property rather than a peripheral adaptation. Finally, we found that the unexpectedly strong contribution of the naive CD5(low) T cell pool showed that the overall self-reactive response has not only a diverse polyclonal TCR repertoire, but also comprises a broad range of affinities for self., (Copyright © 2015 by The American Association of Immunologists, Inc.)

Published
2015
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44. Premature expression of Foxp3 in double-negative thymocytes.

Author

Barra MM, Richards DM, Hofer AC, Delacher M, and Feuerer M

Subjects
Animals, Flow Cytometry, Forkhead Transcription Factors physiology, Gene Expression genetics, Gene Expression physiology, Hepatocyte Nuclear Factor 1-alpha deficiency, Hepatocyte Nuclear Factor 1-alpha physiology, Mice, Mice, Inbred C57BL, Polymerase Chain Reaction, Receptors, Antigen, T-Cell metabolism, Forkhead Transcription Factors metabolism, Thymocytes metabolism
Abstract

Peripheral immune regulation depends on the generation of thymic-derived regulatory T (tTreg) cells to maintain self-tolerance and to counterbalance overshooting immune responses. The expression of the Treg lineage defining transcription factor Foxp3 in developing tTreg cells depends on TCR signaling during the thymic selection process of these T cells. In this study, we surprisingly identify Foxp3+ immature thymocytes at the double-negative (DN) stage in transcription factor 7 (Tcf7)-deficient mice. These Foxp3+ cells did not express a TCR (β or γδ chains), CD3 or CD5 and therefore these cells were true DN cells. Further investigation of this phenomenon in a transgenic TCR model showed that Foxp3-expressing DN cells could not respond to TCR stimulation in vivo. These data suggest that Foxp3 expression in these DN cells occurred independently of TCR signaling. Interestingly, these Foxp3+ DN cells were located in a transition state between DN1 and DN2 (CD4-CD8-CD3-TCR-CD44highCD25low). Our results indicate that Tcf7 is involved in preventing the premature expression of Foxp3 in DN thymocytes.

Published
2015
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45. Brown adipose tissue harbors a distinct sub-population of regulatory T cells.

Author

Medrikova D, Sijmonsma TP, Sowodniok K, Richards DM, Delacher M, Sticht C, Gretz N, Schafmeier T, Feuerer M, and Herzig S

Subjects
Adipose Tissue, Brown metabolism, Adipose Tissue, Brown pathology, Animals, Female, Gene Expression Profiling, Gene Expression Regulation, Inflammation genetics, Inflammation immunology, Inflammation metabolism, Metabolic Networks and Pathways, Metabolome, Metabolomics methods, Mice, Phenotype, Spleen cytology, Spleen immunology, Spleen metabolism, T-Lymphocyte Subsets metabolism, T-Lymphocytes, Regulatory metabolism, Adipose Tissue, Brown immunology, T-Lymphocyte Subsets immunology, T-Lymphocytes, Regulatory immunology
Abstract

Regulatory T (Treg) cells are critical determinants of both immune responses and metabolic control. Here we show that systemic ablation of Treg cells compromised the adaptation of whole-body energy expenditure to cold exposure, correlating with impairment in thermogenic marker gene expression and massive invasion of pro-inflammatory macrophages in brown adipose tissue (BAT). Indeed, BAT harbored a unique sub-set of Treg cells characterized by a unique gene signature. As these Treg cells respond to BAT activation upon cold exposure, this study defines a BAT-specific Treg sub-set with direct implications for the regulation of energy homeostasis in response to environmental stress.

Published
2015
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46. Treg Cell Differentiation: From Thymus to Peripheral Tissue.

Author

Richards DM, Delacher M, Goldfarb Y, Kägebein D, Hofer AC, Abramson J, and Feuerer M

Subjects
Humans, Models, Immunological, Cell Differentiation, T-Lymphocytes, Regulatory cytology, Thymus Gland cytology
Abstract

Regulatory T cells (Tregs) are crucial mediators of self-tolerance in the periphery. They differentiate in the thymus, where interactions with thymus-resident antigen-presenting cells, an instructive cytokine milieu, and stimulation of the T cell receptor lead to the selection into the Treg lineage and the induction of Foxp3 gene expression. Once mature, Treg cells leave the thymus and migrate into either the secondary lymphoid tissues, e.g., lymph nodes and spleen, or peripheral nonlymphoid tissues. There is growing evidence that Treg cells go beyond the classical modulation of immune responses and also play important functional roles in nonlymphoid peripheral tissues. In this review, we summarize recent findings about the thymic Treg lineage differentiation as well as the further specialization of Treg cells in the secondary lymphoid and in the peripheral nonlymphoid organs., (© 2015 Elsevier Inc. All rights reserved.)

Published
2015
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47. Love is in the Aire: mTECs share their assets.

Author

Kyewski B and Feuerer M

Subjects
Animals, AIRE Protein, Bone Marrow Cells immunology, Receptors, Antigen, T-Cell, alpha-beta immunology, Self Tolerance immunology, Thymus Gland immunology, Transcription Factors genetics
Abstract

Self-tolerance imposition requires the presentation of self-antigens by a variety of thymic antigen-presenting cells. In this issue of Immunity, Perry et al. (2014) reveal unidirectional self-antigen transfer from medullary thymic epithelial cells to dendritic cells as an essential aspect., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Published
2014
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48. Transcriptional control of regulatory T cells.

Author

Delacher M, Schreiber L, Richards DM, Farah C, Feuerer M, and Huehn J

Subjects
Animals, Cell Differentiation, Humans, Signal Transduction, T-Lymphocytes, Regulatory cytology, Transcription Factors genetics, T-Lymphocytes, Regulatory metabolism, Transcription Factors metabolism, Transcription, Genetic
Abstract

Regulatory T cells (Tregs) constitute unique T cell lineage that plays a key role for immunological tolerance. Tregs are characterized by the expression of the forkhead box transcription factor Foxp3, which acts as a lineage-specifying factor by determining the unique suppression profile of these immune cells. Here, we summarize the recent progress in understanding how Foxp3 expression itself is epigenetically and transcriptionally controlled, how the Treg-specific signature is achieved and how unique properties of Treg subsets are defined by other transcription factors. Finally, we will discuss recent studies focusing on the molecular targeting of Tregs to utilize the specific properties of this unique cell type in therapeutic settings.

Published
2014
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49. Monocytes and macrophages in cancer: development and functions.

Author

Richards DM, Hettinger J, and Feuerer M

Abstract

Monocytes and tumor-associated macrophages are part of the myeloid family, a group of hematopoietic derived cells. Monocytes are direct precursors of hematopoietic stem cell-derived macrophages. After their recruitment into the tumor tissue, they can differentiate into tumor-associated macrophages, a very heterogeneous cell population in terms of phenotype and pro-tumor function, supporting tumor initiation, local progression and distant metastasis. Therefore, targeting monocytes and macrophages is a promising immunotherapeutic approach. This review will focus on the development of monocytes as macrophage precursors, the functions of tumor-associated macrophages and the possibility of interfering with tumor development and progression by targeting these myeloid cells.

Published
2013
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50. Origin of monocytes and macrophages in a committed progenitor.

Author

Hettinger J, Richards DM, Hansson J, Barra MM, Joschko AC, Krijgsveld J, and Feuerer M

Subjects
Animals, Cell Differentiation immunology, Chromatography, Liquid, Female, Male, Mice, Mice, Inbred C57BL, Monocyte-Macrophage Precursor Cells cytology, Specific Pathogen-Free Organisms, Spectrometry, Mass, Electrospray Ionization, Spleen cytology, Tandem Mass Spectrometry, Bone Marrow immunology, Monocyte-Macrophage Precursor Cells immunology, Proteomics methods, Spleen immunology
Abstract

Monocytes, macrophages and dendritic cells (DCs) are developmentally related regulators of the immune system that share the monocyte-macrophage DC progenitor (MDP) as a common precursor. Unlike differentiation into DCs, the distal pathways for differentiation into monocytes and monocyte-derived macrophages are not fully elucidated. We have now demonstrated the existence of a clonogenic, monocyte- and macrophage-restricted progenitor cell derived from the MDP. This progenitor was a Ly6C(+) proliferating cell present in the bone marrow and spleen that generated the major monocyte subsets and macrophages, but not DCs or neutrophils. By in-depth quantitative proteomics, we characterized changes in the proteome during monocyte differentiation, which provided insight into the molecular principles of developing monocytes, such as their functional maturation. Thus, we found that monocytes and macrophages were renewed independently of DCs from a committed progenitor.

Published
2013
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