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462 results on '"Ginhoux, F."'

1. Apolipoprotein E controls Dectin-1-dependent development of monocyte-derived alveolar macrophages upon pulmonary β-glucan-induced inflammatory adaptation

Author

Theobald, H., Bejarano, D. A., Katzmarski, N., Haub, J., Schulte-Schrepping, J., Yu, J., Bassler, K., Ament, A. L., Osei-Sarpong, C., Piattini, F., Vornholz, L., T’Jonck, W., Györfi, A. H., Hayer, H., Yu, X., Sheoran, S., Al Jawazneh, A., Chakarov, S., Haendler, K., Brown, G. D., Williams, D. L., Bosurgi, L., Distler, J. H. W., Ginhoux, F., Ruland, J., Beyer, M. D., Greter, M., Bain, C. C., Vazquez-Armendariz, A. I., Kopf, M., Schultze, J. L., and Schlitzer, A.

Published
2024
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2. Response to contamination of isolated mouse Kupffer cells with liver sinusoidal endothelial cells

Author

Iannacone, M, Blériot, C, Andreata, F, Ficht, X, Laura, C, Garcia-Manteiga, J, Uderhardt, S, Ginhoux, F, Iannacone M., Blériot C., Andreata F., Ficht X., Laura C., Garcia-Manteiga J. M., Uderhardt S., Ginhoux F., Iannacone, M, Blériot, C, Andreata, F, Ficht, X, Laura, C, Garcia-Manteiga, J, Uderhardt, S, Ginhoux, F, Iannacone M., Blériot C., Andreata F., Ficht X., Laura C., Garcia-Manteiga J. M., Uderhardt S., and Ginhoux F.

Published
2022

4. Single-cell protein expression profiling resolves circulating and resident memory T cell diversity across tissues and infection contexts

Author

Evrard, M, Becht, E, Fonseca, R, Obers, A, Park, SL, Ghabdan-Zanluqui, N, Schroeder, J, Christo, SN, Schienstock, D, Lai, J, Burn, TN, Clatch, A, House, IG, Beavis, P, Kallies, A, Ginhoux, F, Mueller, SN, Gottardo, R, Newell, EW, Mackay, LK, Evrard, M, Becht, E, Fonseca, R, Obers, A, Park, SL, Ghabdan-Zanluqui, N, Schroeder, J, Christo, SN, Schienstock, D, Lai, J, Burn, TN, Clatch, A, House, IG, Beavis, P, Kallies, A, Ginhoux, F, Mueller, SN, Gottardo, R, Newell, EW, and Mackay, LK

Abstract

Memory CD8+ T cells can be broadly divided into circulating (TCIRCM) and tissue-resident memory T (TRM) populations. Despite well-defined migratory and transcriptional differences, the phenotypic and functional delineation of TCIRCM and TRM cells, particularly across tissues, remains elusive. Here, we utilized an antibody screening platform and machine learning prediction pipeline (InfinityFlow) to profile >200 proteins in TCIRCM and TRM cells in solid organs and barrier locations. High-dimensional analyses revealed unappreciated heterogeneity within TCIRCM and TRM cell lineages across nine different organs after either local or systemic murine infection models. Additionally, we demonstrated the relative effectiveness of strategies allowing for the selective ablation of TCIRCM or TRM populations across organs and identified CD55, KLRG1, CXCR6, and CD38 as stable markers for characterizing memory T cell function during inflammation. Together, these data and analytical framework provide an in-depth resource for memory T cell classification in both steady-state and inflammatory conditions.

Published
2023

7. Apolipoprotein E controls Dectin-1-dependent development of monocyte-derived alveolar macrophages upon pulmonary β-glucan-induced inflammatory adaptation

Author

Theobald, H., primary, Bejarano, D.A., additional, Katzmarski, N., additional, Haub, J., additional, Schulte-Schrepping, J., additional, Yu, J., additional, Bassler, K, additional, Ćirović, B., additional, Osei-Sarpong, C., additional, Piattini, F., additional, Vornholz, L, additional, Yu, X., additional, Sheoran, S., additional, Al Jawazneh, A., additional, Chakarov, S., additional, Haendler, K, additional, Brown, G.D., additional, Williams, D.L., additional, Bosurgi, L., additional, Ginhoux, F., additional, Ruland, J., additional, Beyer, M., additional, Greter, M., additional, Kopf, M., additional, Schultze, J.L., additional, and Schlitzer, A., additional

Published
2022
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8. A subset of Kupffer cells regulates metabolism through the expression of CD36

Author

Bleriot, C, Barreby, E, Dunsmore, G, Ballaire, R, Chakarov, S, Ficht, X, De Simone, G, Andreata, F, Fumagalli, V, Guo, W, Wan, G, Gessain, G, Khalilnezhad, A, Zhang, X, Ang, N, Chen, P, Morgantini, C, Azzimato, V, Kong, W, Liu, Z, Pai, R, Lum, J, Shihui, F, Low, I, Xu, C, Malleret, B, Kairi, M, Balachander, A, Cexus, O, Larbi, A, Lee, B, Newell, E, Ng, L, Phoo, W, Sobota, R, Sharma, A, Howland, S, Chen, J, Bajenoff, M, Yvan-Charvet, L, Venteclef, N, Iannacone, M, Aouadi, M, Ginhoux, F, Bleriot C., Barreby E., Dunsmore G., Ballaire R., Chakarov S., Ficht X., De Simone G., Andreata F., Fumagalli V., Guo W., Wan G., Gessain G., Khalilnezhad A., Zhang X. M., Ang N., Chen P., Morgantini C., Azzimato V., Kong W. T., Liu Z., Pai R., Lum J., Shihui F., Low I., Xu C., Malleret B., Kairi M. F. M., Balachander A., Cexus O., Larbi A., Lee B., Newell E. W., Ng L. G., Phoo W. W., Sobota R. M., Sharma A., Howland S. W., Chen J., Bajenoff M., Yvan-Charvet L., Venteclef N., Iannacone M., Aouadi M., Ginhoux F., Bleriot, C, Barreby, E, Dunsmore, G, Ballaire, R, Chakarov, S, Ficht, X, De Simone, G, Andreata, F, Fumagalli, V, Guo, W, Wan, G, Gessain, G, Khalilnezhad, A, Zhang, X, Ang, N, Chen, P, Morgantini, C, Azzimato, V, Kong, W, Liu, Z, Pai, R, Lum, J, Shihui, F, Low, I, Xu, C, Malleret, B, Kairi, M, Balachander, A, Cexus, O, Larbi, A, Lee, B, Newell, E, Ng, L, Phoo, W, Sobota, R, Sharma, A, Howland, S, Chen, J, Bajenoff, M, Yvan-Charvet, L, Venteclef, N, Iannacone, M, Aouadi, M, Ginhoux, F, Bleriot C., Barreby E., Dunsmore G., Ballaire R., Chakarov S., Ficht X., De Simone G., Andreata F., Fumagalli V., Guo W., Wan G., Gessain G., Khalilnezhad A., Zhang X. M., Ang N., Chen P., Morgantini C., Azzimato V., Kong W. T., Liu Z., Pai R., Lum J., Shihui F., Low I., Xu C., Malleret B., Kairi M. F. M., Balachander A., Cexus O., Larbi A., Lee B., Newell E. W., Ng L. G., Phoo W. W., Sobota R. M., Sharma A., Howland S. W., Chen J., Bajenoff M., Yvan-Charvet L., Venteclef N., Iannacone M., Aouadi M., and Ginhoux F.

Abstract

Tissue macrophages are immune cells whose phenotypes and functions are dictated by origin and niches. However, tissues are complex environments, and macrophage heterogeneity within the same organ has been overlooked so far. Here, we used high-dimensional approaches to characterize macrophage populations in the murine liver. We identified two distinct populations among embryonically derived Kupffer cells (KCs) sharing a core signature while differentially expressing numerous genes and proteins: a major CD206loESAM– population (KC1) and a minor CD206hiESAM+ population (KC2). KC2 expressed genes involved in metabolic processes, including fatty acid metabolism both in steady-state and in diet-induced obesity and hepatic steatosis. Functional characterization by depletion of KC2 or targeted silencing of the fatty acid transporter Cd36 highlighted a crucial contribution of KC2 in the liver oxidative stress associated with obesity. In summary, our study reveals that KCs are more heterogeneous than anticipated, notably describing a subpopulation wired with metabolic functions.

Published
2021

9. Identification of a Kupffer cell subset capable of reverting the T cell dysfunction induced by hepatocellular priming

Author

De Simone, G, Andreata, F, Bleriot, C, Fumagalli, V, Laura, C, Garcia-Manteiga, J, Di Lucia, P, Gilotto, S, Ficht, X, De Ponti, F, Bono, E, Giustini, L, Ambrosi, G, Mainetti, M, Zordan, P, Benechet, A, Rava, M, Chakarov, S, Moalli, F, Bajenoff, M, Guidotti, L, Ginhoux, F, Iannacone, M, De Simone G., Andreata F., Bleriot C., Fumagalli V., Laura C., Garcia-Manteiga J. M., Di Lucia P., Gilotto S., Ficht X., De Ponti F. F., Bono E. B., Giustini L., Ambrosi G., Mainetti M., Zordan P., Benechet A. P., Rava M., Chakarov S., Moalli F., Bajenoff M., Guidotti L. G., Ginhoux F., Iannacone M., De Simone, G, Andreata, F, Bleriot, C, Fumagalli, V, Laura, C, Garcia-Manteiga, J, Di Lucia, P, Gilotto, S, Ficht, X, De Ponti, F, Bono, E, Giustini, L, Ambrosi, G, Mainetti, M, Zordan, P, Benechet, A, Rava, M, Chakarov, S, Moalli, F, Bajenoff, M, Guidotti, L, Ginhoux, F, Iannacone, M, De Simone G., Andreata F., Bleriot C., Fumagalli V., Laura C., Garcia-Manteiga J. M., Di Lucia P., Gilotto S., Ficht X., De Ponti F. F., Bono E. B., Giustini L., Ambrosi G., Mainetti M., Zordan P., Benechet A. P., Rava M., Chakarov S., Moalli F., Bajenoff M., Guidotti L. G., Ginhoux F., and Iannacone M.

Abstract

Kupffer cells (KCs) are highly abundant, intravascular, liver-resident macrophages known for their scavenger and phagocytic functions. KCs can also present antigens to CD8+ T cells and promote either tolerance or effector differentiation, but the mechanisms underlying these discrepant outcomes are poorly understood. Here, we used a mouse model of hepatitis B virus (HBV) infection, in which HBV-specific naive CD8+ T cells recognizing hepatocellular antigens are driven into a state of immune dysfunction, to identify a subset of KCs (referred to as KC2) that cross-presents hepatocellular antigens upon interleukin-2 (IL-2) administration, thus improving the antiviral function of T cells. Removing MHC-I from all KCs, including KC2, or selectively depleting KC2 impaired the capacity of IL-2 to revert the T cell dysfunction induced by intrahepatic priming. In summary, by sensing IL-2 and cross-presenting hepatocellular antigens, KC2 overcome the tolerogenic potential of the hepatic microenvironment, suggesting new strategies for boosting hepatic T cell immunity.

Published
2021

10. 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

11. Transitional premonocytes emerge in the periphery for host defense against bacterial infections

Author

Teh, YC, Chooi, MY, Liu, D, Kwok, I, Lai, GC, Yong, LAO, Ng, M, Li, JLY, Tan, Y, Evrard, M, Tan, L, Liong, KH, Leong, K, Goh, CC, Chan, AYJ, Shadan, NB, Mantri, CK, Hwang, YY, Cheng, H, Cheng, T, Yu, W, Tey, HL, Larbi, A, St John, A, Angeli, V, Ruedl, C, Lee, B, Ginhoux, F, Chen, SL, Ng, LG, Ding, JL, Chong, SZ, Teh, YC, Chooi, MY, Liu, D, Kwok, I, Lai, GC, Yong, LAO, Ng, M, Li, JLY, Tan, Y, Evrard, M, Tan, L, Liong, KH, Leong, K, Goh, CC, Chan, AYJ, Shadan, NB, Mantri, CK, Hwang, YY, Cheng, H, Cheng, T, Yu, W, Tey, HL, Larbi, A, St John, A, Angeli, V, Ruedl, C, Lee, B, Ginhoux, F, Chen, SL, Ng, LG, Ding, JL, and Chong, SZ

Abstract

Circulating Ly6Chi monocytes often undergo cellular death upon exhaustion of their antibacterial effector functions, which limits their capacity for subsequent macrophage differentiation. This shrouds the understanding on how the host replaces the tissue-resident macrophage niche effectively during bacterial invasion to avert infection morbidity. Here, we show that proliferating transitional premonocytes (TpMos), an immediate precursor of mature Ly6Chi monocytes (MatMos), were mobilized into the periphery in response to acute bacterial infection and sepsis. TpMos were less susceptible to apoptosis and served as the main source of macrophage replenishment when MatMos were vulnerable toward bacteria-induced cellular death. Furthermore, TpMo and its derived macrophages contributed to host defense by balancing the proinflammatory cytokine response of MatMos. Consequently, adoptive transfer of TpMos improved the survival outcome of lethal sepsis. Our findings hence highlight a protective role for TpMos during bacterial infections and their contribution toward monocyte-derived macrophage heterogeneity in distinct disease outcomes.

Published
2022

12. Notch-dependent cooperativity between myeloid lineages promotes Langerhans cell histiocytosis pathology

Author

Kvedaraite E, Milne P, Khalilnezhad A, Chevrier M, Sethi R, Lee HK, Hagey DW, von Bahr Greenwood T, Mouratidou N, Jadersten M, Lee NYS, Minnerup L, Yingrou T, Dutertre C-A, Benac N, Hwang YY, Lum J, Loh AHP, Jansson J, Teng KWW, Khalilnezhad S, Weili X, Resteu A, Liang TH, Guan NL, Larbi A, Howland SW, Arnell H, Andaloussi SEL, Braier J, Rassidakis G, Galluzzo L, Dzionek A, Henter JI, Chen J, Collin M, Ginhoux F

Published
2022
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13. Dynamics and genomic landscape of CD8+ T cells undergoing hepatic priming

Author

Benechet, A, De Simone, G, Di Lucia, P, Cilenti, F, Barbiera, G, Le Bert, N, Fumagalli, V, Lusito, E, Moalli, F, Bianchessi, V, Andreata, F, Zordan, P, Bono, E, Giustini, L, Bonilla, W, Bleriot, C, Kunasegaran, K, Gonzalez-Aseguinolaza, G, Pinschewer, D, Kennedy, P, Naldini, L, Kuka, M, Ginhoux, F, Cantore, A, Bertoletti, A, Ostuni, R, Guidotti, L, Iannacone, M, Benechet A. P., De Simone G., Di Lucia P., Cilenti F., Barbiera G., Le Bert N., Fumagalli V., Lusito E., Moalli F., Bianchessi V., Andreata F., Zordan P., Bono E., Giustini L., Bonilla W. V., Bleriot C., Kunasegaran K., Gonzalez-Aseguinolaza G., Pinschewer D. D., Kennedy P. T. F., Naldini L., Kuka M., Ginhoux F., Cantore A., Bertoletti A., Ostuni R., Guidotti L. G., Iannacone M., Benechet, A, De Simone, G, Di Lucia, P, Cilenti, F, Barbiera, G, Le Bert, N, Fumagalli, V, Lusito, E, Moalli, F, Bianchessi, V, Andreata, F, Zordan, P, Bono, E, Giustini, L, Bonilla, W, Bleriot, C, Kunasegaran, K, Gonzalez-Aseguinolaza, G, Pinschewer, D, Kennedy, P, Naldini, L, Kuka, M, Ginhoux, F, Cantore, A, Bertoletti, A, Ostuni, R, Guidotti, L, Iannacone, M, Benechet A. P., De Simone G., Di Lucia P., Cilenti F., Barbiera G., Le Bert N., Fumagalli V., Lusito E., Moalli F., Bianchessi V., Andreata F., Zordan P., Bono E., Giustini L., Bonilla W. V., Bleriot C., Kunasegaran K., Gonzalez-Aseguinolaza G., Pinschewer D. D., Kennedy P. T. F., Naldini L., Kuka M., Ginhoux F., Cantore A., Bertoletti A., Ostuni R., Guidotti L. G., and Iannacone M.

Abstract

The responses of CD8+ T cells to hepatotropic viruses such as hepatitis B range from dysfunction to differentiation into effector cells, but the mechanisms that underlie these distinct outcomes remain poorly understood. Here we show that priming by Kupffer cells, which are not natural targets of hepatitis B, leads to differentiation of CD8+ T cells into effector cells that form dense, extravascular clusters of immotile cells scattered throughout the liver. By contrast, priming by hepatocytes, which are natural targets of hepatitis B, leads to local activation and proliferation of CD8+ T cells but not to differentiation into effector cells; these cells form loose, intravascular clusters of motile cells that coalesce around portal tracts. Transcriptomic and chromatin accessibility analyses reveal unique features of these dysfunctional CD8+ T cells, with limited overlap with those of exhausted or tolerant T cells; accordingly, CD8+ T cells primed by hepatocytes cannot be rescued by treatment with anti-PD-L1, but instead respond to IL-2. These findings suggest immunotherapeutic strategies against chronic hepatitis B infection.

Published
2019

14. Isolation of mouse Kupffer cells for phenotypic and functional studies

Author

Andreata, F, Blériot, C, Di Lucia, P, De Simone, G, Fumagalli, V, Ficht, X, Beccaria, C, Kuka, M, Ginhoux, F, Iannacone, M, Andreata, Francesco, Blériot, Camille, Di Lucia, Pietro, De Simone, Giorgia, Fumagalli, Valeria, Ficht, Xenia, Beccaria, Cristian Gabriel, Kuka, Mirela, Ginhoux, Florent, Iannacone, Matteo, Andreata, F, Blériot, C, Di Lucia, P, De Simone, G, Fumagalli, V, Ficht, X, Beccaria, C, Kuka, M, Ginhoux, F, Iannacone, M, Andreata, Francesco, Blériot, Camille, Di Lucia, Pietro, De Simone, Giorgia, Fumagalli, Valeria, Ficht, Xenia, Beccaria, Cristian Gabriel, Kuka, Mirela, Ginhoux, Florent, and Iannacone, Matteo

Abstract

Here, we provide detailed protocols for the isolation of mouse Kupffer cells – the liver-resident macrophages – for phenotypic (e.g., via flow cytometry, mass cytometry, or RNA-sequencing) analyses or for functional experiments involving cell culture. The procedures presented can be adapted for the isolation of other hepatic cell populations. For complete details on the use and execution of this protocol, please refer to De Simone et al. (2021).

Published
2021

16. OA01.06 Randomised Phase 2 Study of Nivolumab (N) Versus Nivolumab and Ipilimumab (NI) Combination in EGFR Mutant NSCLC

Author

Lai, G., primary, Alvarez, J., additional, Yeo, J.C., additional, Sim, N.L., additional, Tan, A., additional, Zhou, S., additional, Suteja, L., additional, Lim, T.W., additional, Rohatgi, N., additional, Yeong, J., additional, Takano, A., additional, Lim, K.H.T., additional, Gogna, A., additional, Too, C.W., additional, Zhuang, K.D., additional, Jain, A., additional, Tan, W., additional, Kanesvaran, R., additional, Ng, Q.S., additional, Ang, M., additional, Rajasekaran, T., additional, Wang, L., additional, Toh, C.K., additional, Lim, W., additional, Tam, W.L., additional, Ginhoux, F., additional, Tan, S.H., additional, Skanderup, A., additional, Tan, D., additional, and Tan, E., additional

Published
2021
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17. Perturbation of the immune cells and prenatal neurogenesis by the triplication of the Erg gene in mouse models of Down syndrome

Author

Ishihara, K, Shimizu, R, Takata, K, Kawashita, E, Amano, K, Shimohata, A, Low, D, Nabe, T, Sago, H, Alexander, WS, Ginhoux, F, Yamakawa, K, Akiba, S, Ishihara, K, Shimizu, R, Takata, K, Kawashita, E, Amano, K, Shimohata, A, Low, D, Nabe, T, Sago, H, Alexander, WS, Ginhoux, F, Yamakawa, K, and Akiba, S

Abstract

Some mouse models of Down syndrome (DS), including Ts1Cje mice, exhibit impaired prenatal neurogenesis with yet unknown molecular mechanism. To gain insights into the impaired neurogenesis, a transcriptomic and flow cytometry analysis of E14.5 Ts1Cje embryo brain was performed. Our analysis revealed that the neutrophil and monocyte ratios in the CD45-positive hematopoietic cells were relatively increased, in agreement with the altered expression of inflammation/immune-related genes, in Ts1Cje embryonic brain, whereas the relative number of brain macrophages was decreased in comparison to wild-type mice. Similar upregulation of inflammation-associated mRNAs was observed in other DS mouse models, with variable trisomic region lengths. We used genetic manipulation to assess the contribution of Erg, a trisomic gene in these DS models, known to regulation hemato-immune cells. The perturbed proportions of immune cells in Ts1Cje mouse brain were restored in Ts1Cje-Erg+/+/Mld2 mice, which are disomic for functional Erg but otherwise trisomic on a Ts1Cje background. Moreover, the embryonic neurogenesis defects observed in Ts1Cje cortex were reduced in Ts1Cje-Erg+/+/Mld2 embryos. Our findings suggest that Erg gene triplication contributes to the dysregulation of the homeostatic proportion of the populations of immune cells in the embryonic brain and decreased prenatal cortical neurogenesis in the prenatal brain with DS.

Published
2020

23. AB0050 EXTENDED POLYDIMENSIONAL IMMUNOME CHARACTERISATION (EPIC) PLATFORM AS A TOOL FOR TRANSLATIONAL RESEARCH

Author

Yeo, J. G., primary, Wasser, M., additional, Kumar, P., additional, Pan, L., additional, Poh, S. L., additional, Ally, F., additional, Arkachaisri, T., additional, Lim, A. J. M., additional, Leong, J. Y., additional, Yeo, K. T., additional, Lai, L., additional, Lee, E. S. C., additional, Chua, C., additional, Paleja, B., additional, Tang, S. P., additional, Ng, S. K., additional, Tan, A. Y. J., additional, Lee, S. Y., additional, Ginhoux, F., additional, Ng, T. P., additional, Larbi, A., additional, and Albani, S., additional

Published
2020
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24. Single-Cell Analysis of Human Mononuclear Phagocytes Reveals Subset-Defining Markers and Identifies Circulating Inflammatory Dendritic Cells

Author

Dutertre, C.-A. Becht, E. Irac, S.E. Khalilnezhad, A. Narang, V. Khalilnezhad, S. Ng, P.Y. van den Hoogen, L.L. Leong, J.Y. Lee, B. Chevrier, M. Zhang, X.M. Yong, P.J.A. Koh, G. Lum, J. Howland, S.W. Mok, E. Chen, J. Larbi, A. Tan, H.K.K. Lim, T.K.H. Karagianni, P. Tzioufas, A.G. Malleret, B. Brody, J. Albani, S. van Roon, J. Radstake, T. Newell, E.W. Ginhoux, F.

Abstract

Human mononuclear phagocytes comprise phenotypically and functionally overlapping subsets of dendritic cells (DCs) and monocytes, but the extent of their heterogeneity and distinct markers for subset identification remains elusive. By integrating high-dimensional single-cell protein and RNA expression data, we identified distinct markers to delineate monocytes from conventional DC2 (cDC2s). Using CD88 and CD89 for monocytes and HLA-DQ and FcεRIα for cDC2s allowed for their specific identification in blood and tissues. We also showed that cDC2s could be subdivided into phenotypically and functionally distinct subsets based on CD5, CD163, and CD14 expression, including a distinct subset of circulating inflammatory CD5−CD163+CD14+ cells related to previously defined DC3s. These inflammatory DC3s were expanded in systemic lupus erythematosus patients and correlated with disease activity. These findings further unravel the heterogeneity of DC subpopulations in health and disease and may pave the way for the identification of specific DC subset-targeting therapies. Using high-dimensional protein and RNA single-cell analyses, Dutertre et al. analyze human dendritic cell and monocyte subsets and identify markers that delineate them and unravel their heterogeneity. They also reveal the presence of inflammatory CD14+ DC3s, a subset of cDC2s, that correlate with disease progression and may be functionally involved in systemic lupus erythematosus immunopathology. © 2019 Elsevier Inc.

Published
2019

25. 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

28. A Liver Capsular Network of Monocyte-Derived Macrophages Restricts Hepatic Dissemination of Intraperitoneal Bacteria by Neutrophil Recruitment

Author

Sierro, F, Evrard, M, Rizzetto, S, Melino, M, Mitchell, AJ, Florido, M, Beattie, L, Walters, SB, Tay, SS, Lu, B, Holz, LE, Roediger, B, Wong, YC, Warren, A, Ritchie, W, McGuffog, C, Weninger, W, Le Couteur, DG, Ginhoux, F, Britton, WJ, Heath, WR, Saunders, BM, McCaughan, GW, Luciani, F, MacDonald, KPA, Ng, LG, Bowen, DG, Bertolino, P, Sierro, F, Evrard, M, Rizzetto, S, Melino, M, Mitchell, AJ, Florido, M, Beattie, L, Walters, SB, Tay, SS, Lu, B, Holz, LE, Roediger, B, Wong, YC, Warren, A, Ritchie, W, McGuffog, C, Weninger, W, Le Couteur, DG, Ginhoux, F, Britton, WJ, Heath, WR, Saunders, BM, McCaughan, GW, Luciani, F, MacDonald, KPA, Ng, LG, Bowen, DG, and Bertolino, P

Abstract

© 2017 Elsevier Inc. The liver is positioned at the interface between two routes traversed by pathogens in disseminating infection. Whereas blood-borne pathogens are efficiently cleared in hepatic sinusoids by Kupffer cells (KCs), it is unknown how the liver prevents dissemination of peritoneal pathogens accessing its outer membrane. We report here that the hepatic capsule harbors a contiguous cellular network of liver-resident macrophages phenotypically distinct from KCs. These liver capsular macrophages (LCMs) were replenished in the steady state from blood monocytes, unlike KCs that are embryonically derived and self-renewing. LCM numbers increased after weaning in a microbiota-dependent process. LCMs sensed peritoneal bacteria and promoted neutrophil recruitment to the capsule, and their specific ablation resulted in decreased neutrophil recruitment and increased intrahepatic bacterial burden. Thus, the liver contains two separate and non-overlapping niches occupied by distinct resident macrophage populations mediating immunosurveillance at these two pathogen entry points to the liver.

Published
2017

30. Unsupervised High-Dimensional Analysis Aligns Dendritic Cells across Tissues and Species

Author

Guilliams, M. (Martin), Dutertre, C.-A. (Charles-Antoine), Scott, C.L. (C.), McGovern, N. (Naomi), Sichien, D. (Dorine), Chakarov, S. (Svetoslav), Van Gassen, S. (Sofie), Chen, J. (Jinmiao), Poidinger, M. (Michael), Prijck, S. (Sofie) de, Tavernier, S.J. (Simon), Low, I. (Ivy), Irac, S.E. (Sergio Erdal), Mattar, C.N. (Citra Nurfarah), Sumatoh, H.R. (Hermi Rizal), Low, G.H.L. (Gillian Hui Ling), Chung, T.J.K. (Tam John Kit), Chan, D.K.H. (Dedrick Kok Hong), Tan, K.K. (Ker Kan), Hon, T.L.K. (Tony Lim Kiat), Fossum, E. (Even), Bogen, B. (Bjarne), Choolani, M. (Mahesh), Chan, J.K.Y. (Jerry Kok Yen), Larbi, A. (Anis), Luche, H. (Hervé), Henri, S. (Sandrine), Saeys, Y. (Yvan), Newell, E.W. (Evan William), Lambrecht, B.N.M. (Bart), Malissen, B. (Bernard), Ginhoux, F. (Florent), Guilliams, M. (Martin), Dutertre, C.-A. (Charles-Antoine), Scott, C.L. (C.), McGovern, N. (Naomi), Sichien, D. (Dorine), Chakarov, S. (Svetoslav), Van Gassen, S. (Sofie), Chen, J. (Jinmiao), Poidinger, M. (Michael), Prijck, S. (Sofie) de, Tavernier, S.J. (Simon), Low, I. (Ivy), Irac, S.E. (Sergio Erdal), Mattar, C.N. (Citra Nurfarah), Sumatoh, H.R. (Hermi Rizal), Low, G.H.L. (Gillian Hui Ling), Chung, T.J.K. (Tam John Kit), Chan, D.K.H. (Dedrick Kok Hong), Tan, K.K. (Ker Kan), Hon, T.L.K. (Tony Lim Kiat), Fossum, E. (Even), Bogen, B. (Bjarne), Choolani, M. (Mahesh), Chan, J.K.Y. (Jerry Kok Yen), Larbi, A. (Anis), Luche, H. (Hervé), Henri, S. (Sandrine), Saeys, Y. (Yvan), Newell, E.W. (Evan William), Lambrecht, B.N.M. (Bart), Malissen, B. (Bernard), and Ginhoux, F. (Florent)

Abstract

Dendritic cells (DCs) are professional antigen-presenting cells that hold great therapeutic potential. Multiple DC subsets have been described, and it remains challenging to align them across tissues and species to analyze their function in the absence of macrophage contamination. Here, we provide and validate a universal toolbox for the automated identification of DCs through unsupervised analysis of conventional flow cytometry and mass cytometry data obtained from multiple mouse, macaque, and human tissues. The use of a minimal set of lineage-imprinted markers was sufficient to subdivide DCs into conventional type 1 (cDC1s), conventional type 2 (cDC2s), and plasmacytoid DCs (pDCs) across tissues and species. This way, a large number of additional markers can still be used to further characterize the heterogeneity of DCs across tissues and during inflammation. This framework represents the way forward to a universal, high-throughput, and standardized analysis of DC populations from mutant mice and human patients.

Published
2016
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32. CXCR4 identifies transitional bone marrow premonocytes that replenish the mature monocyte pool for peripheral responses

Author

Chong, SZ, Evrard, M, Devi, S, Chen, J, Lim, JY, See, P, Zhang, Y, Adrover, JM, Lee, B, Tan, L, Li, JLY, Liong, KH, Phua, C, Balachander, A, Boey, A, Liebl, D, Tan, SM, Chan, JKY, Balabanian, K, Harris, JE, Bianchini, M, Weber, C, Duchene, J, Lum, J, Poidinger, M, Chen, Q, Renia, L, Wang, C-I, Larbi, A, Randolph, GJ, Weninger, W, Looney, MR, Krummel, MF, Biswas, SK, Ginhoux, F, Hidalgo, A, Bachelerie, F, Ng, LG, Chong, SZ, Evrard, M, Devi, S, Chen, J, Lim, JY, See, P, Zhang, Y, Adrover, JM, Lee, B, Tan, L, Li, JLY, Liong, KH, Phua, C, Balachander, A, Boey, A, Liebl, D, Tan, SM, Chan, JKY, Balabanian, K, Harris, JE, Bianchini, M, Weber, C, Duchene, J, Lum, J, Poidinger, M, Chen, Q, Renia, L, Wang, C-I, Larbi, A, Randolph, GJ, Weninger, W, Looney, MR, Krummel, MF, Biswas, SK, Ginhoux, F, Hidalgo, A, Bachelerie, F, and Ng, LG

Abstract

It is well established that Ly6Chi monocytes develop from common monocyte progenitors (cMoPs) and reside in the bone marrow (BM) until they are mobilized into the circulation. In our study, we found that BM Ly6Chi monocytes are not a homogenous population, as current data would suggest. Using computational analysis approaches to interpret multidimensional datasets, we demonstrate that BM Ly6Chi monocytes consist of two distinct subpopulations (CXCR4hi and CXCR4lo subpopulations) in both mice and humans. Transcriptome studies and in vivo assays revealed functional differences between the two subpopulations. Notably, the CXCR4hi subset proliferates and is immobilized in the BM for the replenishment of functionally mature CXCR4lo monocytes. We propose that the CXCR4hi subset represents a transitional premonocyte population, and that this sequential step of maturation from cMoPs serves to maintain a stable pool of BM monocytes. Additionally, reduced CXCR4 expression on monocytes, upon their exit into the circulation, does not reflect its diminished role in monocyte biology. Specifically, CXCR4 regulates monocyte peripheral cellular activities by governing their circadian oscillations and pulmonary margination, which contributes toward lung injury and sepsis mortality. Together, our study demonstrates the multifaceted role of CXCR4 in defining BM monocyte heterogeneity and in regulating their function in peripheral tissues.

Published
2016

33. Intravital multiphoton imaging of mouse tibialis anterior muscle.

Author

Lau, J, Goh, CC, Devi, S, Keeble, J, See, P, Ginhoux, F, Ng, LG, Lau, J, Goh, CC, Devi, S, Keeble, J, See, P, Ginhoux, F, and Ng, LG

Abstract

Intravital imaging by multiphoton microscopy is a powerful tool to gain invaluable insight into tissue biology and function. Here, we provide a step-by-step tissue preparation protocol for imaging the mouse tibialis anterior skeletal muscle. Additionally, we include steps for jugular vein catheterization that allow for well-controlled intravenous reagent delivery. Preparation of the tibialis anterior muscle is minimally invasive, reducing the chances of inducing damage and inflammation prior to imaging. The tibialis anterior muscle is useful for imaging leukocyte interaction with vascular endothelium, and to understand muscle contraction biology. Importantly, this model can be easily adapted to study neuromuscular diseases and myopathies.

Published
2016

35. Unsupervised High-Dimensional Analysis Aligns Dendritic Cells across Tissues and Species

Author

Guilliams, M, Dutertre, C A, Scott, CL, McGovern, N, Sichien, D, Chakarov, S, Van Gassen, S, Chen, JM, Poidinger, M, De Prijck, S, Tavernier, SJ, Low, I, Irac, S E, Mattar, C N, Sumatoh, H R, Low, G H L, Chung, T J K, Chan, D K H, Tan, K K, Hon, T L K, Fossum, E, Bogen, B, Choolani, M, Chan, J K Y, Larbi, A, Luche, H, Henri, S, Saeys, Y, Newell, E W, Lambrecht, Bart, Malissen, B, Ginhoux, F, Guilliams, M, Dutertre, C A, Scott, CL, McGovern, N, Sichien, D, Chakarov, S, Van Gassen, S, Chen, JM, Poidinger, M, De Prijck, S, Tavernier, SJ, Low, I, Irac, S E, Mattar, C N, Sumatoh, H R, Low, G H L, Chung, T J K, Chan, D K H, Tan, K K, Hon, T L K, Fossum, E, Bogen, B, Choolani, M, Chan, J K Y, Larbi, A, Luche, H, Henri, S, Saeys, Y, Newell, E W, Lambrecht, Bart, Malissen, B, and Ginhoux, F

Published
2016

36. IRF8 mutations and human dendritic-cell immunodeficiency

Author

Hambleton S, Salem S, Bustamante J, Bigley V, Boisson-Dupuis S, Azevedo J, Fortin A, Haniffa M, Ceron-Gutierrez L, Bacon CM, Menon G, Trouillet C, McDonald D, Carey P, Ginhoux F, Alsina L, Zumwalt TJ, Kong XF, Kumararatne D, Butler K, Hubeau M, Feinberg J, Al-Muhsen S, Cant A, Abel L, Chaussabel D, Doffinger R, Talesnik E, Grumach A, Duarte A, Abarca K, Moraes-Vasconcelos D, Burk D, Berghuis A, Geissmann F, Collin M, Casanova JL, and Gros P

Published
2011

37. Liver inflammation abrogates T cell mediated tolerance against particulate antigens induced by liver Kupffer cells

Author

Heymann, F, primary, Peusquens, J, additional, Ludwig-Portugall, I, additional, Kohlhepp, M, additional, Ergen, C, additional, Niemietz, P, additional, Martin, C, additional, van Roojen, N, additional, Ochando, J, additional, Randolph, G, additional, Luedde, T, additional, Ginhoux, F, additional, Kurts, C, additional, Trautwein, C, additional, and Tacke, F, additional

Published
2015
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38. A unique role for p53 in the regulation of M2 macrophage polarization

Author

Li, L, primary, Ng, D S W, additional, Mah, W-C, additional, Almeida, F F, additional, Rahmat, S A, additional, Rao, V K, additional, Leow, S C, additional, Laudisi, F, additional, Peh, M T, additional, Goh, A M, additional, Lim, J S Y, additional, Wright, G D, additional, Mortellaro, A, additional, Taneja, R, additional, Ginhoux, F, additional, Lee, C G, additional, Moore, P K, additional, and Lane, D P, additional

Published
2014
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41. CSF-1-Dependant M2 Macrophages Mediate Chronic Graft-Versus-Host Disease.

Author

Alexander, K., primary, Flynn, R., additional, Lineburg, K., additional, Kuns, R., additional, Janela, B., additional, Teal, B., additional, Olver, S., additional, Lor, M., additional, Raffelt, N., additional, Koyama, M., additional, Leveque, L., additional, Le Texier, L., additional, Melino, M., additional, Markey, K., additional, Varelias, A., additional, Ginhoux, F., additional, Engwerda, C., additional, Clouston, A., additional, Blazer, B., additional, Hill, G., additional, and MacDonald, K., additional

Published
2014
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42. Neutrophil mobilization via plerixafor-mediated CXCR4 inhibition arises from lung demargination and blockade of neutrophil homing to the bone marrow

Author

Devi, S, Wang, Y, Chew, WK, Lima, R, A-Gonzalez, N, Mattar, CNZ, Chong, SZ, Schlitzer, A, Bakocevic, N, Chew, S, Keeble, JL, Goh, CC, Li, JLY, Evrard, M, Malleret, B, Larbi, A, Renia, L, Haniffa, M, Tan, SM, Chan, JKY, Balabanian, K, Nagasawa, T, Bachelerie, F, Hidalgo, A, Ginhoux, F, Kubes, P, Ng, LG, Devi, S, Wang, Y, Chew, WK, Lima, R, A-Gonzalez, N, Mattar, CNZ, Chong, SZ, Schlitzer, A, Bakocevic, N, Chew, S, Keeble, JL, Goh, CC, Li, JLY, Evrard, M, Malleret, B, Larbi, A, Renia, L, Haniffa, M, Tan, SM, Chan, JKY, Balabanian, K, Nagasawa, T, Bachelerie, F, Hidalgo, A, Ginhoux, F, Kubes, P, and Ng, LG

Abstract

Blood neutrophil homeostasis is essential for successful host defense against invading pathogens. Circulating neutrophil counts are positively regulated by CXCR2 signaling and negatively regulated by the CXCR4-CXCL12 axis. In particular, G-CSF, a known CXCR2 signaler, and plerixafor, a CXCR4 antagonist, have both been shown to correct neutropenia in human patients. G-CSF directly induces neutrophil mobilization from the bone marrow (BM) into the blood, but the mechanisms underlying plerixafor-induced neutrophilia remain poorly defined. Using a combination of intravital multiphoton microscopy, genetically modified mice and novel in vivo homing assays, we demonstrate that G-CSF and plerixafor work through distinct mechanisms. In contrast to G-CSF, CXCR4 inhibition via plerixafor does not result in neutrophil mobilization from the BM. Instead, plerixafor augments the frequency of circulating neutrophils through their release from the marginated pool present in the lung, while simultaneously preventing neutrophil return to the BM. Our study demonstrates for the first time that drastic changes in blood neutrophils can originate from alternative reservoirs other than the BM, while implicating a role for CXCR4-CXCL12 interactions in regulating lung neutrophil margination. Collectively, our data provides valuable insights into the fundamental regulation of neutrophil homeostasis, which may lead to the development of improved treatment regimens for neutropenic patients.

Published
2013

43. Adult Langerhans cells derive predominantly from embryonic fetal liver monocytes with a minor contribution of yolk sac-derived macrophages.

Author

Hoeffel, G, Wang, Y, Greter, M, See, P, Teo, P, Malleret, B, Leboeuf, M, Low, D, Oller, G, Almeida, F, Choy, SHY, Grisotto, M, Renia, L, Conway, SJ, Stanley, ER, Chan, JKY, Ng, LG, Samokhvalov, IM, Merad, M, Ginhoux, F, Hoeffel, G, Wang, Y, Greter, M, See, P, Teo, P, Malleret, B, Leboeuf, M, Low, D, Oller, G, Almeida, F, Choy, SHY, Grisotto, M, Renia, L, Conway, SJ, Stanley, ER, Chan, JKY, Ng, LG, Samokhvalov, IM, Merad, M, and Ginhoux, F

Abstract

Langerhans cells (LCs) are the dendritic cells (DCs) of the epidermis, forming one of the first hematopoietic lines of defense against skin pathogens. In contrast to other DCs, LCs arise from hematopoietic precursors that seed the skin before birth. However, the origin of these embryonic precursors remains unclear. Using in vivo lineage tracing, we identify a first wave of yolk sac (YS)-derived primitive myeloid progenitors that seed the skin before the onset of fetal liver hematopoiesis. YS progenitors migrate to the embryo proper, including the prospective skin, where they give rise to LC precursors, and the brain rudiment, where they give rise to microglial cells. However, in contrast to microglia, which remain of YS origin throughout life, YS-derived LC precursors are largely replaced by fetal liver monocytes during late embryogenesis. Consequently, adult LCs derive predominantly from fetal liver monocyte-derived cells with a minor contribution of YS-derived cells. Altogether, we establish that adult LCs have a dual origin, bridging early embryonic and late fetal myeloid development.

Published
2012

48. A unique role for p53 in the regulation of M2 macrophage polarization.

Author

Li, L, Ng, D S W, Mah, W-C, Almeida, F F, Rahmat, S A, Rao, V K, Leow, S C, Laudisi, F, Peh, M T, Goh, A M, Lim, J S Y, Wright, G D, Mortellaro, A, Taneja, R, Ginhoux, F, Lee, C G, Moore, P K, and Lane, D P

Subjects
MACROPHAGE activation, POLARIZATION microscopy, GENE expression, LIPOPOLYSACCHARIDES, ESCHERICHIA coli
Abstract

P53 is critically important in preventing oncogenesis but its role in inflammation in general and in the function of inflammatory macrophages in particular is not clear. Here, we show that bone marrow-derived macrophages exhibit endogenous p53 activity, which is increased when macrophages are polarized to the M2 (alternatively activated macrophage) subtype. This leads to reduced expression of M2 genes. Nutlin-3a, which destabilizes the p53/MDM2 (mouse double minute 2 homolog) complex, promotes p53 activation and further downregulates M2 gene expression. In contrast, increased expression of M2 genes was apparent in M2-polarized macrophages from p53-deficient and p53 mutant mice. Furthermore, we show, in mice, that p53 also regulates M2 polarization in peritoneal macrophages from interleukin-4-challenged animals and that nutlin-3a retards the development of tolerance to Escherichia coli lipopolysaccharide. P53 acts via transcriptional repression of expression of c-Myc (v-myc avian myelocytomatosis viral oncogene homolog) gene by directly associating with its promoter. These data establish a role for the p53/MDM2/c-MYC axis as a physiological 'brake' to the M2 polarization process. This work reveals a hitherto unknown role for p53 in macrophages, provides further insight into the complexities of macrophage plasticity and raises the possibility that p53-activating drugs, many of which are currently being trialled clinically, may have unforeseen effects on macrophage function. [ABSTRACT FROM AUTHOR]

Published
2015
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