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3. A recombinant Der p 1-specific allergen-toxin demonstrates superior killing of allergen-reactive IgG+ hybridomas in comparison to its recombinant allergen-drug conjugate

Author

Daramola, A K, primary, Akinrinmade, O A, additional, Fajemisin, E A, additional, Naran, K, additional, Mthembu, N, additional, Hadebe, S, additional, Brombacher, F, additional, Huysamen, A M, additional, Fadeyi, O E, additional, Hunter, R, additional, and Barth, S, additional

Published
2022
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5. Author Correction: Homeostatic IL-13 in healthy skin directs dendritic cell differentiation to promote TH2 and inhibit TH17 cell polarization.

Author

Mayer, JU, Hilligan, KL, Chandler, JS, Eccles, DA, Old, SI, Domingues, RG, Yang, J, Webb, GR, Munoz-Erazo, L, Hyde, EJ, Wakelin, KA, Tang, S-C, Chappell, SC, von Daake, S, Brombacher, F, Mackay, CR, Sher, A, Tussiwand, R, Connor, LM, Gallego-Ortega, D, Jankovic, D, Le Gros, G, Hepworth, MR, Lamiable, O, Ronchese, F, Mayer, JU, Hilligan, KL, Chandler, JS, Eccles, DA, Old, SI, Domingues, RG, Yang, J, Webb, GR, Munoz-Erazo, L, Hyde, EJ, Wakelin, KA, Tang, S-C, Chappell, SC, von Daake, S, Brombacher, F, Mackay, CR, Sher, A, Tussiwand, R, Connor, LM, Gallego-Ortega, D, Jankovic, D, Le Gros, G, Hepworth, MR, Lamiable, O, and Ronchese, F

Abstract

In the version of this article initially published, there were labeling errors in Fig. 8. In Fig. 8a, the top row, now reading “GSE43184:CD1c+ lung versus blood,” originally appeared as “GSE35457….” The bottom row, now reading “GSE35457: CD1c+ skin versus blood,” originally appeared as “GSE43184: CD1c+ lung versus blood.” In Fig. 8b, the top-left plot, now reading “skin versus blood,” originally appeared as “lung versus blood.” The errors have been corrected in the HTML and PDF versions of the article.

Published
2022

7. Homeostatic IL-13 in healthy skin directs dendritic cell differentiation to promote TH2 and inhibit TH17 cell polarization

Author

Mayer, JU, Hilligan, KL, Chandler, JS, Eccles, DA, Old, SI, Domingues, RG, Yang, J, Webb, GR, Munoz-Erazo, L, Hyde, EJ, Wakelin, KA, Tang, S-C, Chappell, SC, von Daake, S, Brombacher, F, Mackay, CR, Sher, A, Tussiwand, R, Connor, LM, Gallego-Ortega, D, Jankovic, D, Le Gros, G, Hepworth, MR, Lamiable, O, and Ronchese, F

Subjects
Mice, Knockout, Mice, Inbred BALB C, CD11b Antigen, Interleukin-13, integumentary system, Immunology, Cell Differentiation, Cell Communication, Allergens, Mice, Inbred C57BL, Phenotype, Th2 Cells, 1107 Immunology, Langerhans Cells, Databases, Genetic, Animals, Humans, Th17 Cells, STAT6 Transcription Factor, Transcriptome, Cells, Cultured, Signal Transduction, Skin
Abstract

The signals driving the adaptation of type 2 dendritic cells (DC2s) to diverse peripheral environments remain mostly undefined. We show that differentiation of CD11blo migratory DC2s-a DC2 population unique to the dermis-required IL-13 signaling dependent on the transcription factors STAT6 and KLF4, whereas DC2s in lung and small intestine were STAT6-independent. Similarly, human DC2s in skin expressed an IL-4 and IL-13 gene signature that was not found in blood, spleen and lung DCs. In mice, IL-13 was secreted homeostatically by dermal innate lymphoid cells and was independent of microbiota, TSLP or IL-33. In the absence of IL-13 signaling, dermal DC2s were stable in number but remained CD11bhi and showed defective activation in response to allergens, with diminished ability to support the development of IL-4+GATA3+ helper T cells (TH), whereas antifungal IL-17+RORγt+ TH cells were increased. Therefore, homeostatic IL-13 fosters a noninflammatory skin environment that supports allergic sensitization.

Published
2021

8. Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network

Author

Grapotte M., Saraswat M., Bessiere C., Menichelli C., Ramilowski J. A., Severin J., Hayashizaki Y., Itoh M., Tagami M., Murata M., Kojima-Ishiyama M., Noma S., Noguchi S., Kasukawa T., Hasegawa A., Suzuki H., Nishiyori-Sueki H., Frith M. C., Abugessaisa I., Aitken S., Aken B. L., Alam I., Alam T., Alasiri R., Alhendi A. M. N., Alinejad-Rokny H., Alvarez M. J., Andersson R., Arakawa T., Araki M., Arbel T., Archer J., Archibald A. L., Arner E., Arner P., Asai K., Ashoor H., Astrom G., Babina M., Baillie J. K., Bajic V. B., Bajpai A., Baker S., Baldarelli R. M., Balic A., Bansal M., Batagov A. O., Batzoglou S., Beckhouse A. G., Beltrami A. P., Beltrami C. A., Bertin N., Bhattacharya S., Bickel P. J., Blake J. A., Blanchette M., Bodega B., Bonetti A., Bono H., Bornholdt J., Bttcher M., Bougouffa S., Boyd M., Breda J., Brombacher F., Brown J. B., Bult C. J., Burroughs A. M., Burt D. W., Busch A., Caglio G., Califano A., Cameron C. J., Cannistraci C. V., Carbone A., Carlisle A. J., Carninci P., Carter K. W., Cesselli D., Chang J. -C., Chen J. C., Chen Y., Chierici M., Christodoulou J., Ciani Y., Clark E. L., Coskun M., Dalby M., Dalla E., Daub C. O., Davis C. A., de Hoon M. J. L., de Rie D., Denisenko E., Deplancke B., Detmar M., Deviatiiarov R., Di Bernardo D., Diehl A. D., Dieterich L. C., Dimont E., Djebali S., Dohi T., Dostie J., Drablos F., Edge A. S. B., Edinger M., Ehrlund A., Ekwall K., Elofsson A., Endoh M., Enomoto H., Enomoto S., Faghihi M., Fagiolini M., Farach-Carson M. C., Faulkner G. J., Favorov A., Fernandes A. M., Ferrai C., Forrest A. R. R., Forrester L. M., Forsberg M., Fort A., Francescatto M., Freeman T. C., Frith M., Fukuda S., Funayama M., Furlanello C., Furuno M., Furusawa C., Gao H., Gazova I., Gebhard C., Geier F., Geijtenbeek T. B. H., Ghosh S., Ghosheh Y., Gingeras T. R., Gojobori T., Goldberg T., Goldowitz D., Gough J., Greco D., Gruber A. J., Guhl S., Guigo R., Guler R., Gusev O., Gustincich S., Ha T. J., Haberle V., Hale P., Hallstrom B. M., Hamada M., Handoko L., Hara M., Harbers M., Harrow J., Harshbarger J., Hase T., Hashimoto K., Hatano T., Hattori N., Hayashi R., Herlyn M., Hettne K., Heutink P., Hide W., Hitchens K. J., Sui S. H., 't Hoen P. A. C., Hon C. C., Hori F., Horie M., Horimoto K., Horton P., Hou R., Huang E., Huang Y., Hugues R., Hume D., Ienasescu H., Iida K., Ikawa T., Ikemura T., Ikeo K., Inoue N., Ishizu Y., Ito Y., Ivshina A. V., Jankovic B. R., Jenjaroenpun P., Johnson R., Jorgensen M., Jorjani H., Joshi A., Jurman G., Kaczkowski B., Kai C., Kaida K., Kajiyama K., Kaliyaperumal R., Kaminuma E., Kanaya T., Kaneda H., Kapranov P., Kasianov A. S., Katayama T., Kato S., Kawaguchi S., Kawai J., Kawaji H., Kawamoto H., Kawamura Y. I., Kawasaki S., Kawashima T., Kempfle J. S., Kenna T. J., Kere J., Khachigian L., Kiryu H., Kishima M., Kitajima H., Kitamura T., Kitano H., Klaric E., Klepper K., Klinken S. P., Kloppmann E., Knox A. J., Kodama Y., Kogo Y., Kojima M., Kojima S., Komatsu N., Komiyama H., Kono T., Koseki H., Koyasu S., Kratz A., Kukalev A., Kulakovskiy I., Kundaje A., Kunikata H., Kuo R., Kuo T., Kuraku S., Kuznetsov V. A., Kwon T. J., Larouche M., Lassmann T., Law A., Le-Cao K. -A., Lecellier C. -H., Lee W., Lenhard B., Lennartsson A., Li K., Li R., Lilje B., Lipovich L., Lizio M., Lopez G., Magi S., Mak G. K., Makeev V., Manabe R., Mandai M., Mar J., Maruyama K., Maruyama T., Mason E., Mathelier A., Matsuda H., Medvedeva Y. A., Meehan T. F., Mejhert N., Meynert A., Mikami N., Minoda A., Miura H., Miyagi Y., Miyawaki A., Mizuno Y., Morikawa H., Morimoto M., Morioka M., Morishita S., Moro K., Motakis E., Motohashi H., Mukarram A. K., Mummery C. L., Mungall C. J., Murakawa Y., Muramatsu M., Nagasaka K., Nagase T., Nakachi Y., Nakahara F., Nakai K., Nakamura K., Nakamura Y., Nakazawa T., Nason G. P., Nepal C., Nguyen Q. H., Nielsen L. K., Nishida K., Nishiguchi K. M., Nishiyori H., Nitta K., Notredame C., Ogishima S., Ohkura N., Ohno H., Ohshima M., Ohtsu T., Okada Y., Okada-Hatakeyama M., Okazaki Y., Oksvold P., Orlando V., Ow G. S., Ozturk M., Pachkov M., Paparountas T., Parihar S. P., Park S. -J., Pascarella G., Passier R., Persson H., Philippens I. H., Piazza S., Plessy C., Pombo A., Ponten F., Poulain S., Poulsen T. M., Pradhan S., Prezioso C., Pridans C., Qin X. -Y., Quackenbush J., Rackham O., Ramilowski J., Ravasi T., Rehli M., Rennie S., Rito T., Rizzu P., Robert C., Roos M., Rost B., Roudnicky F., Roy R., Rye M. B., Sachenkova O., Saetrom P., Sai H., Saiki S., Saito M., Saito A., Sakaguchi S., Sakai M., Sakaue S., Sakaue-Sawano A., Sandelin A., Sano H., Sasamoto Y., Sato H., Saxena A., Saya H., Schafferhans A., Schmeier S., Schmidl C., Schmocker D., Schneider C., Schueler M., Schultes E. A., Schulze-Tanzil G., Semple C. A., Seno S., Seo W., Sese J., Sheng G., Shi J., Shimoni Y., Shin J. W., SimonSanchez J., Sivertsson A., Sjostedt E., Soderhall C., Laurent G. S., Stoiber M. H., Sugiyama D., Summers K. M., Suzuki A. M., Suzuki K., Suzuki M., Suzuki N., Suzuki T., Swanson D. J., Swoboda R. K., Taguchi A., Takahashi H., Takahashi M., Takamochi K., Takeda S., Takenaka Y., Tam K. T., Tanaka H., Tanaka R., Tanaka Y., Tang D., Taniuchi I., Tanzer A., Tarui H., Taylor M. S., Terada A., Terao Y., Testa A. C., Thomas M., Thongjuea S., Tomii K., Triglia E. T., Toyoda H., Tsang H. G., Tsujikawa M., Uhlen M., Valen E., van de Wetering M., van Nimwegen E., Velmeshev D., Verardo R., Vitezic M., Vitting-Seerup K., von Feilitzen K., Voolstra C. R., Vorontsov I. E., Wahlestedt C., Wasserman W. W., Watanabe K., Watanabe S., Wells C. A., Winteringham L. N., Wolvetang E., Yabukami H., Yagi K., Yamada T., Yamaguchi Y., Yamamoto M., Yamamoto Y., Yamanaka Y., Yano K., Yasuzawa K., Yatsuka Y., Yo M., Yokokura S., Yoneda M., Yoshida E., Yoshida Y., Yoshihara M., Young R., Young R. S., Yu N. Y., Yumoto N., Zabierowski S. E., Zhang P. G., Zucchelli S., Zwahlen M., Chatelain C., Brehelin L., Grapotte, M., Saraswat, M., Bessiere, C., Menichelli, C., Ramilowski, J. A., Severin, J., Hayashizaki, Y., Itoh, M., Tagami, M., Murata, M., Kojima-Ishiyama, M., Noma, S., Noguchi, S., Kasukawa, T., Hasegawa, A., Suzuki, H., Nishiyori-Sueki, H., Frith, M. C., Abugessaisa, I., Aitken, S., Aken, B. L., Alam, I., Alam, T., Alasiri, R., Alhendi, A. M. N., Alinejad-Rokny, H., Alvarez, M. J., Andersson, R., Arakawa, T., Araki, M., Arbel, T., Archer, J., Archibald, A. L., Arner, E., Arner, P., Asai, K., Ashoor, H., Astrom, G., Babina, M., Baillie, J. K., Bajic, V. B., Bajpai, A., Baker, S., Baldarelli, R. M., Balic, A., Bansal, M., Batagov, A. O., Batzoglou, S., Beckhouse, A. G., Beltrami, A. P., Beltrami, C. A., Bertin, N., Bhattacharya, S., Bickel, P. J., Blake, J. A., Blanchette, M., Bodega, B., Bonetti, A., Bono, H., Bornholdt, J., Bttcher, M., Bougouffa, S., Boyd, M., Breda, J., Brombacher, F., Brown, J. B., Bult, C. J., Burroughs, A. M., Burt, D. W., Busch, A., Caglio, G., Califano, A., Cameron, C. J., Cannistraci, C. V., Carbone, A., Carlisle, A. J., Carninci, P., Carter, K. W., Cesselli, D., Chang, J. -C., Chen, J. C., Chen, Y., Chierici, M., Christodoulou, J., Ciani, Y., Clark, E. L., Coskun, M., Dalby, M., Dalla, E., Daub, C. O., Davis, C. A., de Hoon, M. J. L., de Rie, D., Denisenko, E., Deplancke, B., Detmar, M., Deviatiiarov, R., Di Bernardo, D., Diehl, A. D., Dieterich, L. C., Dimont, E., Djebali, S., Dohi, T., Dostie, J., Drablos, F., Edge, A. S. B., Edinger, M., Ehrlund, A., Ekwall, K., Elofsson, A., Endoh, M., Enomoto, H., Enomoto, S., Faghihi, M., Fagiolini, M., Farach-Carson, M. C., Faulkner, G. J., Favorov, A., Fernandes, A. M., Ferrai, C., Forrest, A. R. R., Forrester, L. M., Forsberg, M., Fort, A., Francescatto, M., Freeman, T. C., Frith, M., Fukuda, S., Funayama, M., Furlanello, C., Furuno, M., Furusawa, C., Gao, H., Gazova, I., Gebhard, C., Geier, F., Geijtenbeek, T. B. H., Ghosh, S., Ghosheh, Y., Gingeras, T. R., Gojobori, T., Goldberg, T., Goldowitz, D., Gough, J., Greco, D., Gruber, A. J., Guhl, S., Guigo, R., Guler, R., Gusev, O., Gustincich, S., Ha, T. J., Haberle, V., Hale, P., Hallstrom, B. M., Hamada, M., Handoko, L., Hara, M., Harbers, M., Harrow, J., Harshbarger, J., Hase, T., Hashimoto, K., Hatano, T., Hattori, N., Hayashi, R., Herlyn, M., Hettne, K., Heutink, P., Hide, W., Hitchens, K. J., Sui, S. H., 't Hoen, P. A. C., Hon, C. C., Hori, F., Horie, M., Horimoto, K., Horton, P., Hou, R., Huang, E., Huang, Y., Hugues, R., Hume, D., Ienasescu, H., Iida, K., Ikawa, T., Ikemura, T., Ikeo, K., Inoue, N., Ishizu, Y., Ito, Y., Ivshina, A. V., Jankovic, B. R., Jenjaroenpun, P., Johnson, R., Jorgensen, M., Jorjani, H., Joshi, A., Jurman, G., Kaczkowski, B., Kai, C., Kaida, K., Kajiyama, K., Kaliyaperumal, R., Kaminuma, E., Kanaya, T., Kaneda, H., Kapranov, P., Kasianov, A. S., Katayama, T., Kato, S., Kawaguchi, S., Kawai, J., Kawaji, H., Kawamoto, H., Kawamura, Y. I., Kawasaki, S., Kawashima, T., Kempfle, J. S., Kenna, T. J., Kere, J., Khachigian, L., Kiryu, H., Kishima, M., Kitajima, H., Kitamura, T., Kitano, H., Klaric, E., Klepper, K., Klinken, S. P., Kloppmann, E., Knox, A. J., Kodama, Y., Kogo, Y., Kojima, M., Kojima, S., Komatsu, N., Komiyama, H., Kono, T., Koseki, H., Koyasu, S., Kratz, A., Kukalev, A., Kulakovskiy, I., Kundaje, A., Kunikata, H., Kuo, R., Kuo, T., Kuraku, S., Kuznetsov, V. A., Kwon, T. J., Larouche, M., Lassmann, T., Law, A., Le-Cao, K. -A., Lecellier, C. -H., Lee, W., Lenhard, B., Lennartsson, A., Li, K., Li, R., Lilje, B., Lipovich, L., Lizio, M., Lopez, G., Magi, S., Mak, G. K., Makeev, V., Manabe, R., Mandai, M., Mar, J., Maruyama, K., Maruyama, T., Mason, E., Mathelier, A., Matsuda, H., Medvedeva, Y. A., Meehan, T. F., Mejhert, N., Meynert, A., Mikami, N., Minoda, A., Miura, H., Miyagi, Y., Miyawaki, A., Mizuno, Y., Morikawa, H., Morimoto, M., Morioka, M., Morishita, S., Moro, K., Motakis, E., Motohashi, H., Mukarram, A. K., Mummery, C. L., Mungall, C. J., Murakawa, Y., Muramatsu, M., Nagasaka, K., Nagase, T., Nakachi, Y., Nakahara, F., Nakai, K., Nakamura, K., Nakamura, Y., Nakazawa, T., Nason, G. P., Nepal, C., Nguyen, Q. H., Nielsen, L. K., Nishida, K., Nishiguchi, K. M., Nishiyori, H., Nitta, K., Notredame, C., Ogishima, S., Ohkura, N., Ohno, H., Ohshima, M., Ohtsu, T., Okada, Y., Okada-Hatakeyama, M., Okazaki, Y., Oksvold, P., Orlando, V., Ow, G. S., Ozturk, M., Pachkov, M., Paparountas, T., Parihar, S. P., Park, S. -J., Pascarella, G., Passier, R., Persson, H., Philippens, I. H., Piazza, S., Plessy, C., Pombo, A., Ponten, F., Poulain, S., Poulsen, T. M., Pradhan, S., Prezioso, C., Pridans, C., Qin, X. -Y., Quackenbush, J., Rackham, O., Ramilowski, J., Ravasi, T., Rehli, M., Rennie, S., Rito, T., Rizzu, P., Robert, C., Roos, M., Rost, B., Roudnicky, F., Roy, R., Rye, M. B., Sachenkova, O., Saetrom, P., Sai, H., Saiki, S., Saito, M., Saito, A., Sakaguchi, S., Sakai, M., Sakaue, S., Sakaue-Sawano, A., Sandelin, A., Sano, H., Sasamoto, Y., Sato, H., Saxena, A., Saya, H., Schafferhans, A., Schmeier, S., Schmidl, C., Schmocker, D., Schneider, C., Schueler, M., Schultes, E. A., Schulze-Tanzil, G., Semple, C. A., Seno, S., Seo, W., Sese, J., Sheng, G., Shi, J., Shimoni, Y., Shin, J. W., Simonsanchez, J., Sivertsson, A., Sjostedt, E., Soderhall, C., Laurent, G. S., Stoiber, M. H., Sugiyama, D., Summers, K. M., Suzuki, A. M., Suzuki, K., Suzuki, M., Suzuki, N., Suzuki, T., Swanson, D. J., Swoboda, R. K., Taguchi, A., Takahashi, H., Takahashi, M., Takamochi, K., Takeda, S., Takenaka, Y., Tam, K. T., Tanaka, H., Tanaka, R., Tanaka, Y., Tang, D., Taniuchi, I., Tanzer, A., Tarui, H., Taylor, M. S., Terada, A., Terao, Y., Testa, A. C., Thomas, M., Thongjuea, S., Tomii, K., Triglia, E. T., Toyoda, H., Tsang, H. G., Tsujikawa, M., Uhlen, M., Valen, E., van de Wetering, M., van Nimwegen, E., Velmeshev, D., Verardo, R., Vitezic, M., Vitting-Seerup, K., von Feilitzen, K., Voolstra, C. R., Vorontsov, I. E., Wahlestedt, C., Wasserman, W. W., Watanabe, K., Watanabe, S., Wells, C. A., Winteringham, L. N., Wolvetang, E., Yabukami, H., Yagi, K., Yamada, T., Yamaguchi, Y., Yamamoto, M., Yamamoto, Y., Yamanaka, Y., Yano, K., Yasuzawa, K., Yatsuka, Y., Yo, M., Yokokura, S., Yoneda, M., Yoshida, E., Yoshida, Y., Yoshihara, M., Young, R., Young, R. S., Yu, N. Y., Yumoto, N., Zabierowski, S. E., Zhang, P. G., Zucchelli, S., Zwahlen, M., Chatelain, C., Brehelin, L., Institute of Biotechnology, Biosciences, Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Computationnelle (IBC), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Méthodes et Algorithmes pour la Bioinformatique (MAB), Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier (LIRMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), National Institute of Advanced Industrial Science and Technology (AIST), SANOFI Recherche, University of British Columbia (UBC), Experimental Immunology, Infectious diseases, AII - Infectious diseases, Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), and Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Montpellier (UM)

Subjects
0301 basic medicine, General Physics and Astronomy, Genome, Mice, 0302 clinical medicine, Transcription (biology), Promoter Regions, Genetic, Transcription Initiation, Genetic, 0303 health sciences, Multidisciplinary, 1184 Genetics, developmental biology, physiology, High-Throughput Nucleotide Sequencing, Neurodegenerative Diseases, 222 Other engineering and technologies, Genomics, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], humanities, Enhancer Elements, Genetic, Microsatellite Repeat, Transcription Initiation Site, Sequence motif, Transcription Initiation, Human, Enhancer Elements, Neural Networks, Science, 610 Medicine & health, Computational biology, Biology, Article, General Biochemistry, Genetics and Molecular Biology, Promoter Regions, 03 medical and health sciences, Computer, Deep Learning, Tandem repeat, Genetic, Clinical Research, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Machine learning, Genetics, Animals, Humans, Polymorphism, Enhancer, Transcriptomics, Gene, A549 Cell, 030304 developmental biology, Polymorphism, Genetic, Neurodegenerative Disease, Base Sequence, Animal, Genome, Human, Human Genome, Computational Biology, Promoter, General Chemistry, 113 Computer and information sciences, Cap analysis gene expression, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Cardiovascular and Metabolic Diseases, A549 Cells, Minion, Generic health relevance, 3111 Biomedicine, Neural Networks, Computer, 610 Medizin und Gesundheit, 030217 neurology & neurosurgery, FANTOM consortium, Microsatellite Repeats
Abstract

Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism., Nature Communications, 12 (1), ISSN:2041-1723

Published
2020

10. Functional annotation of human long noncoding RNAs via molecular phenotyping (vol 30, pg 1060, 2020)

Author

Ramilowski, JA, Yip, CW, Agrawal, S, Chang, J-C, Ciani, Y, Kulakovskiy, IV, Mendez, M, Ooi, JLC, Ouyang, JF, Parkinson, N, Petri, A, Roos, L, Severin, J, Yasuzawa, K, Abugessaisa, I, Akalin, A, Antonov, IV, Arner, E, Bonetti, A, Bono, H, Borsari, B, Brombacher, F, Cameron, CJF, Cannistraci, CV, Cardenas, R, Cardon, M, Chang, H, Dostie, J, Ducoli, L, Favorov, A, Fort, A, Garrido, D, Gil, N, Gimenez, J, Guler, R, Handoko, L, Harshbarger, J, Hasegawa, A, Hasegawa, Y, Hashimoto, K, Hayatsu, N, Heutink, P, Hirose, T, Imada, EL, Itoh, M, Kaczkowski, B, Kanhere, A, Kawabata, E, Kawaji, H, Kawashima, T, Kelly, ST, Kojima, M, Kondo, N, Koseki, H, Kouno, T, Kratz, A, Kurowska-Stolarska, M, Kwon, ATJ, Leek, J, Lennartsson, A, Lizio, M, Lopez-Redondo, F, Luginbuhl, J, Maeda, S, Makeev, VJ, Marchionni, L, Medvedeva, YA, Minoda, A, Muller, F, Munoz-Aguirre, M, Murata, M, Nishiyori, H, Nitta, KR, Noguchi, S, Noro, Y, Nurtdinov, R, Okazaki, Y, Orlando, V, Paquette, D, Parr, CJC, Rackham, OJL, Rizzu, P, Martinez, DFS, Sandelin, A, Sanjana, P, Semple, CAM, Shibayama, Y, Sivaraman, DM, Suzuki, T, Szumowski, SC, Tagami, M, Taylor, MS, Terao, C, Thodberg, M, Thongjuea, S, Tripathi, V, Ulitsky, I, Verardo, R, Vorontsov, IE, Yamamoto, C, Young, RS, Baillie, JK, Forrest, ARR, Guigo, R, Hoffman, MM, Hon, CC, Kasukawa, T, Kauppinen, S, Kere, J, Lenhard, B, Schneider, C, Suzuki, H, Yagi, K, De Hoon, MJL, Shin, JW, Carninci, P, and Wellcome Trust

Subjects
Genetics & Heredity, Biochemistry & Molecular Biology, Science & Technology, Biotechnology & Applied Microbiology, Bioinformatics, 06 Biological Sciences, Life Sciences & Biomedicine, 11 Medical and Health Sciences
Published
2020

26. Protein kinase C-delta (PKCδ), a marker of inflammation and tuberculosis disease progression in humans, is important for optimal macrophage killing effector functions and survival in mice

Author

Parihar, S P, primary, Ozturk, M, additional, Marakalala, M J, additional, Loots, D T, additional, Hurdayal, R, additional, Maasdorp, D Beukes, additional, Van Reenen, M, additional, Zak, D E, additional, Darboe, F, additional, Penn-Nicholson, A, additional, Hanekom, W A, additional, Leitges, M, additional, Scriba, T J, additional, Guler, R, additional, and Brombacher, F, additional

Published
2018
Full Text
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28. Data Descriptor: FANTOM5 CAGE profiles of human and mouse samples

Author

Noguchi, S, Arakawa, T, Fukuda, S, Furuno, M, Hasegawa, A, Hori, F, Ishikawa-Kato, S, Kaida, K, Kaiho, A, Kanamori-Katayama, M, Kawashima, T, Kojima, M, Kubosaki, A, Manabe, R-I, Murata, M, Nagao-Sato, S, Nakazato, K, Ninomiya, N, Nishiyori-Sueki, H, Noma, S, Saijyo, E, Saka, A, Sakai, M, Simon, C, Suzuki, N, Tagami, M, Watanabe, S, Yoshida, S, Arner, P, Axton, RA, Babina, M, Baillie, JK, Barnett, TC, Beckhouse, AG, Blumenthal, A, Bodega, B, Bonetti, A, Briggs, J, Brombacher, F, Carlisle, AJ, Clevers, HC, Davis, CA, Detmar, M, Dohi, T, Edge, ASB, Edinger, M, Ehrlund, A, Ekwall, K, Endoh, M, Enomoto, H, Eslami, A, Fagiolini, M, Fairbairn, L, Farach-Carson, MC, Faulkner, GJ, Ferrai, C, Fisher, ME, Forrester, LM, Fujita, R, Furusawa, J-I, Geijtenbeek, TB, Gingeras, T, Goldowitz, D, Guhl, S, Guler, R, Gustincich, S, Ha, TJ, Hamaguchi, M, Hara, M, Hasegawa, Y, Herlyn, M, Heutink, P, Hitchens, KJ, Hume, DA, Ikawa, T, Ishizu, Y, Kai, C, Kawamoto, H, Kawamura, YI, Kempfle, JS, Kenna, TJ, Kere, J, Khachigian, LM, Kitamura, T, Klein, S, Klinken, SP, Knox, AJ, Kojima, S, Koseki, H, Koyasu, S, Lee, W, Lennartsson, A, Mackay-sim, A, Mejhert, N, Mizuno, Y, Morikawa, H, Morimoto, M, Moro, K, Morris, KJ, Motohashi, H, Mummery, CL, Nakachi, Y, Nakahara, F, Nakamura, T, Nakamura, Y, Nozaki, T, Ogishima, S, Ohkura, N, Ohno, H, Ohshima, M, Okada-Hatakeyama, M, Okazaki, Y, Orlando, V, Ovchinnikov, DA, Passier, R, Patrikakis, M, Pombo, A, Pradhan-Bhatt, S, Qin, X-Y, Rehli, M, Rizzu, P, Roy, S, Sajantila, A, Sakaguchi, S, Sato, H, Satoh, H, Savvi, S, Saxena, A, Schmidl, C, Schneider, C, Schulze-Tanzil, GG, Schwegmann, A, Sheng, G, Shin, JW, Sugiyama, D, Sugiyama, T, Summers, KM, Takahashi, N, Takai, J, Tanaka, H, Tatsukawa, H, Tomoiu, A, Toyoda, H, van de Wetering, M, van den Berg, LM, Verardo, R, Vijayan, D, Wells, CA, Winteringham, LN, Wolvetang, E, Yamaguchi, Y, Yamamoto, M, Yanagi-Mizuochi, C, Yoneda, M, Yonekura, Y, Zhang, PG, Zucchelli, S, Abugessaisa, I, Arner, E, Harshbarger, J, Kondo, A, Lassmann, T, Lizio, M, Sahin, S, Sengstag, T, Severin, J, Shimoji, H, Suzuki, M, Suzuki, H, Kawai, J, Kondo, N, Itoh, M, Daub, CO, Kasukawa, T, Kawaji, H, Carninci, P, Forrest, ARR, Hayashizaki, Y, Noguchi, S, Arakawa, T, Fukuda, S, Furuno, M, Hasegawa, A, Hori, F, Ishikawa-Kato, S, Kaida, K, Kaiho, A, Kanamori-Katayama, M, Kawashima, T, Kojima, M, Kubosaki, A, Manabe, R-I, Murata, M, Nagao-Sato, S, Nakazato, K, Ninomiya, N, Nishiyori-Sueki, H, Noma, S, Saijyo, E, Saka, A, Sakai, M, Simon, C, Suzuki, N, Tagami, M, Watanabe, S, Yoshida, S, Arner, P, Axton, RA, Babina, M, Baillie, JK, Barnett, TC, Beckhouse, AG, Blumenthal, A, Bodega, B, Bonetti, A, Briggs, J, Brombacher, F, Carlisle, AJ, Clevers, HC, Davis, CA, Detmar, M, Dohi, T, Edge, ASB, Edinger, M, Ehrlund, A, Ekwall, K, Endoh, M, Enomoto, H, Eslami, A, Fagiolini, M, Fairbairn, L, Farach-Carson, MC, Faulkner, GJ, Ferrai, C, Fisher, ME, Forrester, LM, Fujita, R, Furusawa, J-I, Geijtenbeek, TB, Gingeras, T, Goldowitz, D, Guhl, S, Guler, R, Gustincich, S, Ha, TJ, Hamaguchi, M, Hara, M, Hasegawa, Y, Herlyn, M, Heutink, P, Hitchens, KJ, Hume, DA, Ikawa, T, Ishizu, Y, Kai, C, Kawamoto, H, Kawamura, YI, Kempfle, JS, Kenna, TJ, Kere, J, Khachigian, LM, Kitamura, T, Klein, S, Klinken, SP, Knox, AJ, Kojima, S, Koseki, H, Koyasu, S, Lee, W, Lennartsson, A, Mackay-sim, A, Mejhert, N, Mizuno, Y, Morikawa, H, Morimoto, M, Moro, K, Morris, KJ, Motohashi, H, Mummery, CL, Nakachi, Y, Nakahara, F, Nakamura, T, Nakamura, Y, Nozaki, T, Ogishima, S, Ohkura, N, Ohno, H, Ohshima, M, Okada-Hatakeyama, M, Okazaki, Y, Orlando, V, Ovchinnikov, DA, Passier, R, Patrikakis, M, Pombo, A, Pradhan-Bhatt, S, Qin, X-Y, Rehli, M, Rizzu, P, Roy, S, Sajantila, A, Sakaguchi, S, Sato, H, Satoh, H, Savvi, S, Saxena, A, Schmidl, C, Schneider, C, Schulze-Tanzil, GG, Schwegmann, A, Sheng, G, Shin, JW, Sugiyama, D, Sugiyama, T, Summers, KM, Takahashi, N, Takai, J, Tanaka, H, Tatsukawa, H, Tomoiu, A, Toyoda, H, van de Wetering, M, van den Berg, LM, Verardo, R, Vijayan, D, Wells, CA, Winteringham, LN, Wolvetang, E, Yamaguchi, Y, Yamamoto, M, Yanagi-Mizuochi, C, Yoneda, M, Yonekura, Y, Zhang, PG, Zucchelli, S, Abugessaisa, I, Arner, E, Harshbarger, J, Kondo, A, Lassmann, T, Lizio, M, Sahin, S, Sengstag, T, Severin, J, Shimoji, H, Suzuki, M, Suzuki, H, Kawai, J, Kondo, N, Itoh, M, Daub, CO, Kasukawa, T, Kawaji, H, Carninci, P, Forrest, ARR, and Hayashizaki, Y

Abstract

In the FANTOM5 project, transcription initiation events across the human and mouse genomes were mapped at a single base-pair resolution and their frequencies were monitored by CAGE (Cap Analysis of Gene Expression) coupled with single-molecule sequencing. Approximately three thousands of samples, consisting of a variety of primary cells, tissues, cell lines, and time series samples during cell activation and development, were subjected to a uniform pipeline of CAGE data production. The analysis pipeline started by measuring RNA extracts to assess their quality, and continued to CAGE library production by using a robotic or a manual workflow, single molecule sequencing, and computational processing to generate frequencies of transcription initiation. Resulting data represents the consequence of transcriptional regulation in each analyzed state of mammalian cells. Non-overlapping peaks over the CAGE profiles, approximately 200,000 and 150,000 peaks for the human and mouse genomes, were identified and annotated to provide precise location of known promoters as well as novel ones, and to quantify their activities.

Published
2017

29. The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome

Author

Hurst, LD, Ghanbarian, AT, Forrest, ARR, Huminiecki, L, Rehli, M, Kenneth Baillie, J, de Hoon, MJL, Haberle, V, Lassmann, T, Kulakovskiy, IV, Lizio, M, Itoh, M, Andersson, R, Mungall, CJ, Meehan, TF, Schmeier, S, Bertin, N, Jørgensen, M, Dimont, E, Arner, E, Schmidl, C, Schaefer, U, Medvedeva, YA, Plessy, C, Vitezic, M, Severin, J, Semple, CA, Ishizu, Y, Young, RS, Francescatto, M, Alam, I, Albanese, D, Altschuler, GM, Arakawa, T, Archer, JAC, Arner, P, Babina, M, Baker, S, Balwierz, PJ, Beckhouse, AG, Pradhan, SB, Blake, JA, Blumenthal, A, Bodega, B, Bonetti, A, Briggs, J, Brombacher, F, Maxwell Burroughs, A, Califano, A, Cannistraci, CV, Carbajo, D, Chen, Y, Chierici, M, Ciani, Y, Clevers, HC, Dalla, E, Davis, CA, Detmar, M, Diehl, AD, Dohi, T, Drabløs, F, Edge, ASB, Edinger, M, Ekwall, K, Endoh, M, Enomoto, H, Fagiolini, M, Fairbairn, L, and Fang, H

Abstract

© 2015 Hurst et al. X chromosomes are unusual in many regards, not least of which is their nonrandom gene content. The causes of this bias are commonly discussed in the context of sexual antagonism and the avoidance of activity in the male germline. Here, we examine the notion that, at least in some taxa, functionally biased gene content may more profoundly be shaped by limits imposed on gene expression owing to haploid expression of the X chromosome. Notably, if the X, as in primates, is transcribed at rates comparable to the ancestral rate (per promoter) prior to the X chromosome formation, then the X is not a tolerable environment for genes with very high maximal net levels of expression, owing to transcriptional traffic jams. We test this hypothesis using The Encyclopedia of DNA Elements (ENCODE) and data from the Functional Annotation of the Mammalian Genome (FANTOM5) project. As predicted, the maximal expression of human X-linked genes is much lower than that of genes on autosomes: on average, maximal expression is three times lower on the X chromosome than on autosomes. Similarly, autosome-to-X retroposition events are associated with lower maximal expression of retrogenes on the X than seen for X-to-autosome retrogenes on autosomes. Also as expected, X-linked genes have a lesser degree of increase in gene expression than autosomal ones (compared to the human/Chimpanzee common ancestor) if highly expressed, but not if lowly expressed. The traffic jam model also explains the known lower breadth of expression for genes on the X (and the Z of birds), as genes with broad expression are, on average, those with high maximal expression. As then further predicted, highly expressed tissue-specific genes are also rare on the X and broadly expressed genes on the X tend to be lowly expressed, both indicating that the trend is shaped by the maximal expression level not the breadth of expression per se. Importantly, a limit to the maximal expression level explains biased tissue of expression profiles of X-linked genes. Tissues whose tissue-specific genes are very highly expressed (e.g., secretory tissues, tissues abundant in structural proteins) are also tissues in which gene expression is relatively rare on the X chromosome. These trends cannot be fully accounted for in terms of alternative models of biased expression. In conclusion, the notion that it is hard for genes on the Therian X to be highly expressed, owing to transcriptional traffic jams, provides a simple yet robustly supported rationale of many peculiar features of X’s gene content, gene expression, and evolution.

Published
2015

31. The statistical geometry of transcriptome divergence in cell-type evolution and cancer

Author

Liang, C, Alam, I, Albanese, D, Altschuler, G, Andersson, R, Arakawa, T, Archer, J, Arner, E, Arner, P, Babina, M, Baillie, K, Bajic, V, Baker, S, Balic, A, Balwierz, P, Beckhouse, A, Bertin, N, Blake, Ja, Blumenthal, A, Bodega, B, Bonetti, A, Briggs, J, Brombacher, F, Burroughs, M, Califano, A, Cannistraci, C, Carbajo, D, Carninci, P, Chen, Yang, Chierici, M, Ciani, Y, Clevers, H, Dalla, Emiliano, Daub, C, Davis, C, De Hoon, M, De Lima Morais, D, Dermar, M, Diehl, A, Dimont, E, Dohl, T, Drabros, F, Edge, A, Edinger, M, Ekwall, K, Endoh, M, Enomoto, H, Fagiolini, M, Fairbairn, L, Fang, H, Farach Carson, Mc, Faulkner, G, Favorov, A, Fisher, M, Forrest, A, Francescatto, M, Freeman, T, Frith, M, Fujita, R, Fukuda, S, Furlanello, C, Furuno, M, Furusawa, J, Geijtenbeek, Tb, Gibson, A, Gingeras, T, Goldowithz, D, Gough, J, Guhl, S, Guler, R, Gustincich, Stefano, Ha, T, Haberle, V, Hamaguchi, M, Hara, M, Harbers, M, Harshbarger, J, Hasegawa, A, Hasegawa, Y, Hashimoto, T, Hayashizaki, Y, Herlyn, M, Heutink, P, Hide, W, Hitchens, K, Ho Sui, S, Hofmann, O, Hoof, I, Hori, F, Hume, D, Huminiecki, L, Iida, K, Ikawa, T, Ishizu, Y, Itoh, M, Jankovic, B, Jia, H, Jorgensen, M, Joshi, A, Jurman, G, Kaczkowski, B, Kai, C, Kaida, K, Kaiho, A, Kajiyama, K, Kanamori Katayama, M, Kasianov, A, Kasukawa, T, Katayama, S, Kato Ishikawa, S, Kawaguchi, S, Kawai, J, Kawaji, H, Kawamoto, H, Kawamura, Y, Kawashima, T, Kempfle, J, Kenna, T, Kere, J, Khachigian, L, Kitamura, T, Klinken, P, Knox, A, Kojima, M, Kojima, S, Kondo, N, Koseki, H, Koyasu, S, Krampitz, S, Kubosaki, A, Kulakovskiy, I, Kwon, At, Laros, J, Lassmann, T, Lenhard, B, Lennartsson, A, Li, K, Lilji, B, Lipovich, L, Lizio, M, Mackay Sim, A, Makeev, V, Manabe, R, Mar, J, Marchand, B, Mathelier, A, Medvedeva, Y, Meehan, Tf, Mejhert, N, Meynert, A, Mizuno, Y, Morikawa, H, Morimoto, M, Moro, K, Motakis, E, Motohashi, H, Mummery, C, Mungall, Cj, Murata, M, Nagao Sato, S, Nakachi, Y, Nakahara, F, Nakamura, T, Nakamura, Y, Nakazato, K, Ninomiya Fukuda, N, Nishiyori Sueki, H, Noma, S, Nozaki, T, Ogishima, S, Ohkura, N, Ohmiya, H, Ohno, H, Ohshima, M, Okada Hatakeyama, M, Okazaki, Y, Orlando, V, Ovchinnikov, D, Pain, A, Passier, R, Persson, H, Piazza, Silvano, Plessy, C, Pradhan Bhatt, S, Prendergast, J, Rackham, O, Ramilowski, J, Rashid, M, Ravasi, T, Rehli, M, Rizzu, P, Roncador, M, Roy, S, Rye, M, Saijyo, E, Sajantila, A, Saka, A, Sakaguchi, S, Sakai, M, Sandelin, A, Sato, H, Satoh, H, Suzana, S, Alka, S, Schaefer, U, Schmeier, S, Schmidl, C, Schneider, C, Schultes, Ea, Schulze Tanzil, G, Schwegmann, A, Semple, C, Sengstag, T, Severin, J, Sheng, G, Shimoji, H, Shimoni, Y, Shin, J, Simon, C, Sugiyama, D, Sugiyama, T, Summers, K, Suzuki, H, Suzuki, M, Suzuki, N, Swoboda, R, Hoen P, T, Tagami, M, Takahashi, N, Takai, J, Tanaka, H, Tatsukawa, H, Tatum, Z, Taylor, M, Thompson, M, Toyoda, H, Toyoda, T, Valen, E, Van De Wetering, M, Van Den Berg, L, Van Nimwegen, E, Verardo, R, Vijayan, D, Vitezic, M, Vorontzov, I, Wasserman, W, Watanabe, S, Wells, C, Winteringham, L, Wolvetang, E, Wood, Ej, Yamaguchi, Y, Yamamoto, M, Yoneda, M, Yonekura, Y, Yoshida, Shin'Ichirou, Young, R, Zabierowski, Se, Zhang, P, Zhao, X, Zucchelli, Silvia, Forrest, Ar, Wagner, Gp, Hubrecht Institute for Developmental Biology and Stem Cell Research, AII - Amsterdam institute for Infection and Immunity, Infectious diseases, and Experimental Immunology

Subjects
Cell type, General Physics and Astronomy, rna-seq data, phylogenetic networks, Biology, ENCODE, General Biochemistry, Genetics and Molecular Biology, Divergence, Transcriptome, Models, Settore BIO/13 - Biologia Applicata, Neoplasms, Humans, Genetics, Models, Statistical, Multidisciplinary, Statistical model, General Chemistry, Statistical, Biological Evolution, Body plan, Tree structure, Evolutionary biology, Cancer cell
Abstract

In evolution, body plan complexity increases due to an increase in the number of individualized cell types. Yet, there is very little understanding of the mechanisms that produce this form of organismal complexity. One model for the origin of novel cell types is the sister cell-type model. According to this model, each cell type arises together with a sister cell type through specialization from an ancestral cell type. A key prediction of the sister cell-type model is that gene expression profiles of cell types exhibit tree structure. Here we present a statistical model for detecting tree structure in transcriptomic data and apply it to transcriptomes from ENCODE and FANTOM5. We show that transcriptomes of normal cells harbour substantial amounts of hierarchical structure. In contrast, cancer cell lines have less tree structure, suggesting that the emergence of cancer cells follows different principles from that of evolutionary cell-type origination.

Published
2015

32. Natural and vaccine-mediated immunity to Salmonella Typhimurium is impaired by the helminth Nippostrongylus brasiliensis

Author

Bobat, S, Darby, M, Mrdjen, D, Cook, C, Logan, E, Auret, J, Jones, E, Schnoeller, C, Flores-Langarica, A, Ross, EA, Vira, A, Lopez-Macias, C, Henderson, IR, Alexander, J, Brombacher, F, Horsnell, WG, and Cunningham, AF

Subjects
Salmonella typhimurium, ANTIBODY-RESPONSE, Salmonella Vaccines, T-Lymphocytes, Antibodies, Helminth, DENDRITIC CELLS, VIRULENT SALMONELLAE, RS, Mice, Tropical Medicine, Animals, Strongylida Infections, TYPE-2 IMMUNITY, Mice, Inbred BALB C, Science & Technology, T-CELL RESPONSES, IFN-GAMMA, Coinfection, ORAL CHALLENGE, ENTERICA SEROVAR TYPHIMURIUM, 11 Medical And Health Sciences, PROTECTIVE IMMUNITY, 06 Biological Sciences, Antibodies, Bacterial, Immunoglobulin Class Switching, Infectious Diseases, Immunoglobulin G, Cytokines, Parasitology, Immunization, Nippostrongylus, Life Sciences & Biomedicine, SCHISTOSOMA-MANSONI
Abstract

Background The impact of exposure to multiple pathogens concurrently or consecutively on immune function is unclear. Here, immune responses induced by combinations of the bacterium Salmonella Typhimurium (STm) and the helminth Nippostrongylus brasiliensis (Nb), which causes a murine hookworm infection and an experimental porin protein vaccine against STm, were examined. Methodology/Principal Findings Mice infected with both STm and Nb induced similar numbers of Th1 and Th2 lymphocytes compared with singly infected mice, as determined by flow cytometry, although lower levels of secreted Th2, but not Th1 cytokines were detected by ELISA after re-stimulation of splenocytes. Furthermore, the density of FoxP3+ T cells in the T zone of co-infected mice was lower compared to mice that only received Nb, but was greater than those that received STm. This reflected the intermediate levels of IL-10 detected from splenocytes. Co-infection compromised clearance of both pathogens, with worms still detectable in mice weeks after they were cleared in the control group. Despite altered control of bacterial and helminth colonization in co-infected mice, robust extrafollicular Th1 and Th2-reflecting immunoglobulin-switching profiles were detected, with IgG2a, IgG1 and IgE plasma cells all detected in parallel. Whilst extrafollicular antibody responses were maintained in the first weeks after co-infection, the GC response was less than that in mice infected with Nb only. Nb infection resulted in some abrogation of the longer-term development of anti-STm IgG responses. This suggested that prior Nb infection may modulate the induction of protective antibody responses to vaccination. To assess this we immunized mice with porins, which confer protection in an antibody-dependent manner, before challenging with STm. Mice that had resolved a Nb infection prior to immunization induced less anti-porin IgG and had compromised protection against infection. Conclusion These findings demonstrate that co-infection can radically alter the development of protective immunity during natural infection and in response to immunization.

Published
2014

33. beta-Glucan exacerbates allergic airway responses to house dust mite allergen

Author

Hadebe, S, Kirstein, F, Fierens, K, Redelinghuys, P, Murray, GI, Williams, DL, Lambrecht, Bart, Brombacher, F, Brown, GD, Hadebe, S, Kirstein, F, Fierens, K, Redelinghuys, P, Murray, GI, Williams, DL, Lambrecht, Bart, Brombacher, F, and Brown, GD

Abstract

beta-(1,3)-Glucan is present in mould cell walls and frequently detected in house dust mite (HDM) faeces. beta-Glucan exposure is thought to be associated with pulmonary allergic inflammation in mouse and man, although the published data are inconsistent. Here, we show that highly purified beta-glucan exacerbates HDM-induced eosinophilic, T helper 2 type airway responses by acting as an adjuvant, promoting activation, proliferation and polarisation of HDM-specific T cells (1-Der beta T cells). We therefore provide definitive evidence that beta-glucan can influence allergic pulmonary inflammation.

Published
2016

34. Differential roles of epigenetic changes and Foxp3 expression in regulatory T cell-specific transcriptional regulation

Author

Morikawa, H, Ohkura, N, Vandenbon, A, Itoh, M, Nagao Sato, S, Kawaji, H, Lassmann, T, Carninci, P, Hayashizaki, Y, Forrest, Ar, Standley, Dm, Date, H, Sakaguchi, S, FANTOM Consortium (Forrest AR, Rehli, M, Baillie, Jk, de Hoon MJ, Haberle, V, Kulakovskiy, Iv, Lizio, M, Andersson, R, Mungall, Cj, Meehan, Tf, Schmeier, S, Bertin, N, Jørgensen, M, Dimont, E, Arner, E, Schmidl, C, Schaefer, U, Medvedeva, Ya, Plessy, C, Vitezic, M, Severin, J, Semple, Ca, Ishizu, Y, Francescatto, M, Alam, I, Albanese, D, Altschuler, Gm, Archer, Ja, Arner, P, Babina, M, Baker, S, Balwierz, Pj, Beckhouse, Ag, Pradhan Bhatt, S, Blake, Ja, Blumenthal, A, Bodega, B, Bonetti, A, Briggs, J, Brombacher, F, Burroughs, Am, Califano, A, Cannistraci, Cv, Carbajo, D, Chen, Y, Chierici, M, Ciani, Y, Clevers, Hc, Dalla, E, Davis, Ca, Deplancke, B, Detmar, M, Diehl, Ad, Dohi, T, Drabløs, F, Edge, As, Edinger, M, Ekwall, K, Endoh, M, Enomoto, H, Fagiolini, M, Fairbairn, L, Fang, H, Farach Carson MC, Faulkner, Gj, Favorov, Av, Fisher, Me, Frith, Mc, Fujita, R, Fukuda, S, Furlanello, C, Furuno, M, Furusawa, J, Geijtenbeek, Tb, Gibson, A, Gingeras, T, Goldowitz, D, Gough, J, Guhl, S, Guler, R, Gustincich, Stefano, Ha, Tj, Hamaguchi, M, Hara, M, Harbers, M, Harshbarger, J, Hasegawa, A, Hasegawa, Y, Hashimoto, T, Herlyn, M, Hitchens, Kj, Ho Sui SJ, Hofmann, Om, Hoof, I, Hori, F, Huminiecki, L, Iida, K, Ikawa, T, Jankovic, Br, Jia, H, Joshi, A, Jurman, G, Kaczkowski, B, Kai, C, Kaida, K, Kaiho, A, Kajiyama, K, Kanamori Katayama, M, Kasianov, As, Kasukawa, T, Katayama, S, Kato, S, Kawaguchi, S, Kawamoto, H, Kawamura, Yi, Kawashima, T, Kempfle, Js, Kenna, Tj, Kere, J, Khachigian, Lm, Kitamura, T, Klinken, Sp, Knox, Aj, Kojima, M, Kojima, S, Kondo, N, Koseki, H, Koyasu, S, Krampitz, S, Kubosaki, A, Kwon, At, Laros, Jf, Lee, W, Lennartsson, A, Li, K, Lilje, B, Lipovich, L, Mackay Sim, A, Manabe, R, Mar, Jc, Marchand, B, Mathelier, A, Mejhert, N, Meynert, A, Mizuno, Y, Morais, Da, Morimoto, M, Moro, K, Motakis, E, Motohashi, H, Mummery, Cl, Murata, M, Nakachi, Y, Nakahara, F, Nakamura, T, Nakamura, Y, Nakazato, K, van Nimwegen, E, Ninomiya, N, Nishiyori, H, Noma, S, Nozaki, T, Ogishima, S, Ohmiya, H, Ohno, H, Ohshima, M, Okada Hatakeyama, M, Okazaki, Y, Orlando, V, Ovchinnikov, Da, Pain, A, Passier, R, Patrikakis, M, Persson, H, Piazza, S, Prendergast, Jg, Rackham, Oj, Ramilowski, Ja, Rashid, M, Ravasi, T, Rizzu, P, Roncador, M, Roy, S, Rye, Mb, Saijyo, E, Sajantila, A, Saka, A, Sakai, M, Sato, H, Satoh, H, Savvi, S, Saxena, A, Schneider, C, Schultes, Ea, Schulze Tanzil GG, Schwegmann, A, Sengstag, T, Sheng, G, Shimoji, H, Shimoni, Y, Shin, Jw, Simon, C, Sugiyama, D, Sugiyama, T, Suzuki, M, Swoboda, Rk, 't Hoen PA, Tagami, M, Takahashi, N, Takai, J, Tanaka, H, Tatsukawa, H, Tatum, Z, Thompson, M, Toyoda, H, Toyoda, T, Valen, E, van de Wetering, M, van den Berg LM, Verardo, R, Vijayan, D, Vorontsov, Ie, Wasserman, Ww, Watanabe, S, Wells, Ca, Winteringham, Ln, Wolvetang, E, Wood, Ej, Yamaguchi, Y, Yamamoto, M, Yoneda, M, Yonekura, Y, Yoshida, S, Zabierowski, Se, Zhang, Pg, Zhao, X, Zucchelli, S, Summers, Km, Suzuki, H, Daub, Co, Kawai, J, Heutink, P, Hide, W, Freeman, Tc, Lenhard, B, Bajic, Vb, Taylor, Ms, Makeev, Vj, Sandelin, A, Hume, Da, Hayashizaki, Y., AII - Amsterdam institute for Infection and Immunity, Infectious diseases, Experimental Immunology, and Hubrecht Institute for Developmental Biology and Stem Cell Research

Subjects
Transcription, Genetic, Regulatory T cell, T-Lymphocytes, Down-Regulation, chemical and pharmacologic phenomena, Biology, Inbred C57BL, T-Lymphocytes, Regulatory, Epigenesis, Genetic, Mice, Genetic, Settore BIO/13 - Biologia Applicata, medicine, Transcriptional regulation, Animals, Epigenetics, Gene, Inbred BALB C, Genetics, Regulation of gene expression, Mice, Inbred BALB C, Multidisciplinary, Binding Sites, FOXP3, hemic and immune systems, Forkhead Transcription Factors, DNA Methylation, Biological Sciences, Regulatory, Cap analysis gene expression, Mice, Inbred C57BL, medicine.anatomical_structure, Gene Expression Regulation, DNA methylation, Transcription, Epigenesis
Abstract

Naturally occurring regulatory T (Treg) cells, which specifically express the transcription factor forkhead box P3 (Foxp3), are engaged in the maintenance of immunological self-tolerance and homeostasis. By transcriptional start site cluster analysis, we assessed here how genome-wide patterns of DNA methylation or Foxp3 binding sites were associated with Treg-specific gene expression. We found that Treg-specific DNA hypomethylated regions were closely associated with Treg up-regulated transcriptional start site clusters, whereas Foxp3 binding regions had no significant correlation with either up- or down-regulated clusters in nonactivated Treg cells. However, in activated Treg cells, Foxp3 binding regions showed a strong correlation with down-regulated clusters. In accordance with these findings, the above two features of activation-dependent gene regulation in Treg cells tend to occur at different locations in the genome. The results collectively indicate that Treg-specific DNA hypomethylation is instrumental in gene up-regulation in steady state Treg cells, whereas Foxp3 down-regulates the expression of its target genes in activated Treg cells. Thus, the two events seem to play distinct but complementary roles in Treg-specific gene expression.

Published
2014

35. Th2-Induced Airway Mucus Production Is Dependent on IL-4Rα, But Not on Eosinophils

Author

Cohn, L., Robert Homer, Macleod, H., Mohrs, M., Brombacher, F., and Bottomly, K.

Subjects
Immunology, Immunology and Allergy
Abstract

Mucus hyperproduction in asthma results from airway inflammation and contributes to clinical symptoms, airway obstruction, and mortality. In human asthmatics and in animal models, excess mucus production correlates with airway eosinophilia. We previously described a system in which TCR transgenic CD4 Th2 cells generated in vitro were transferred into recipient mice and activated in the respiratory tract with inhaled Ag. Th2 cells stimulated airway eosinophilia and a marked increase in mucus production, while mice that received Th1 cells exhibited airway inflammation without eosinophilia or mucus. Mucus could be induced by IL-4−/− Th2 cells at comparable levels to mucus induced by IL-4+/+ Th2 cells. In the current studies we dissect further the mechanisms of Th2-induced mucus production. When IL-4−/− Th2 cells are transferred into IL-4Rα−/− mice, mucus is not induced, and BAL eosinophilia is absent. These data suggest that in the absence of IL-4, IL-13 may be critical for Th2-induced mucus production and eosinophilia. To determine whether eosinophils are important in mucus production, IL-5−/− Th2 cells were transferred into IL-5−/− recipients. Eosinophilia was abolished, yet mucus staining in the epithelium persisted. These studies show definitively that IL-5, eosinophils, or mast cells are not essential, but signaling through IL-4Rα is critically important in Th2 cell stimulation of mucus production.

Published
1999

39. Microbial ligand costimulation drives neutrophilic steroid-refractory asthma

Author

Hadebe, S, Kirstein, F, Fierens, K, Chen, K, Drummond, RA, Vautier, S, Sajaniemi, S, Murray, G, Williams, DL, Redelinghuys, P, Reinhart, TA, Junecko, BAF, Kolls, JK, Lambrecht, BN, Brombacher, F, Brown, GD, Ryffel, B, Hadebe, S, Kirstein, F, Fierens, K, Chen, K, Drummond, RA, Vautier, S, Sajaniemi, S, Murray, G, Williams, DL, Redelinghuys, P, Reinhart, TA, Junecko, BAF, Kolls, JK, Lambrecht, BN, Brombacher, F, Brown, GD, and Ryffel, B

Abstract

Asthma is a heterogeneous disease whose etiology is poorly understood but is likely to involve innate responses to inhaled microbial components that are found in allergens. The influence of these components on pulmonary inflammation has been largely studied in the context of individual agonists, despite knowledge that they can have synergistic effects when used in combination. Here we have explored the effects of LPS and β-glucan, two commonly-encountered microbial agonists, on the pathogenesis of allergic and non-allergic respiratory responses to house dust mite allergen. Notably, sensitization with these micro-bial components in combination acted synergistically to promote robust neutrophilic inflammation, which involved both Dectin-1 and TLR-4. This pulmonary neutrophilic inflammation was corticosteroid-refractory, resembling that found in patients with severe asthma. Thus our results provide key new insights into how microbial components influence the development of respiratory pathology.

Published
2015

40. IL-4-independent regulation of in vivo IL-9 expression

Author

Monteyne P, Jc, Renauld, Van Broeck J, David Dunne, Brombacher F, Jp, Coutelier, UCL - MD/MIGE - Département de microbiologie, d'immunologie et de génétique, and UCL - (SLuc) Service de microbiologie

Subjects
Mice, Knockout, Mice, Gene Expression Regulation, Immunology, Interleukin-9, Animals, Immunology and Allergy, Interleukin-4, T-Lymphocytes, Helper-Inducer
Abstract

We focused on the role of IL-4 in the regulation of the Th2 cytokine IL-9. In vivo, IL-9 mRNA was detected in lymph nodes after immunization with soluble Ags. IL-9 expression preceded that of IL-4, and was not affected in IL-4 knockout mice. In contrast, a significant decrease of IL-9 message was observed in IL-10-deficient mice, indicating a role for this cytokine in the induction of IL-9 production. Treatment with anti-CD4 Ab and analysis of purified CD4 cells confirmed that IL-9 was produced by CD4+ cells. Moreover, similarly to what has been reported for IL-4, IL-9 message induction was strongly decreased by infection with lactate dehydrogenase-elevating virus. IL-9 mRNA was also detected after in vivo stimulation with anti-CD3 Ab. In this model, IL-9 expression followed that of IL-4, but was not reduced in IL-4-deficient mice. This contrasts with in vitro stimulation in which, as reported in humans, IL-9 expression in lymphocytes incubated with anti-CD3 Ab and costimulatory molecules appeared as a late event, and was partly dependent on IL-4. In vitro IL-9 secretion was reduced significantly by addition of anti-IL-4 Ab, as well as in lymphocytes from IL-4 gene-deficient mice. Taken together, our results indicate that the Th2 cytokine IL-9 can be expressed by both IL-4-dependent and -independent pathways.

Published
1997

44. The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line

Author

FANTOM Consortium, Suzuki H, Forrest AR, van Nimwegen E, Daub CO, Balwierz PJ, Irvine KM, Lassmann T, Ravasi T, Hasegawa Y, de Hoon MJ, Katayama S, Schroder K, Carninci P, Tomaru Y, Kanamori-Katayama M, Kubosaki A, Akalin A, Ando Y, Arner E, Asada M, Asahara H, Bailey T, Bajic VB, Bauer D, Beckhouse AG, Bertin N, Bjxf6rkegren J, Brombacher F, Bulger E, Chalk AM, Chiba J, Cloonan N, Dawe A, Dostie J, Engstrxf6m PG, Essack M, Faulkner GJ, Fink JL, Fredman D, Fujimori K, Furuno M, Gojobori T, Gough J, and Grimmond SM

Published
2009

45. Interleukin-17, a negative regulator in established allergic asthma

Author

Schnyder-Candrian, S., Togbe, Dieudonnée, Couillin, Isabelle, Mercier, I., Brombacher, F., Quesniaux, Valérie, Fossiez, F., Ryffel, Bernhard, Schnyder, B., Immunologie et Embryologie Moléculaires (IEM), and Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.IMM]Life Sciences [q-bio]/Immunology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2006

46. IL-9 protects against bleomycin-induced lung injury: involvement of prostaglandins

Author

Arras, M., Louahed, J., Heilier, J. -F, Delos, M., Brombacher, F., Jean-Christophe Renauld, Lison, D., Huaux, F., UCL - MD/MNOP - Département de morphologie normale et pathologique, UCL - MD/ESP - Ecole de santé publique, UCL - MD/MIGE - Département de microbiologie, d'immunologie et de génétique, UCL - (SLuc) Centre de toxicologie clinique, UCL - (SLuc) Service de biochimie médicale, and UCL - (MGD) Service d'anatomie pathologique

Subjects
Lung Diseases, Time Factors, L-Lactate Dehydrogenase, Indomethacin, Interleukin-9, Mice, Inbred Strains, Mice, Transgenic, Lung Injury, Original Research Paper, Bleomycin, Mice, Water Supply, Prostaglandins, Animals, Bronchoalveolar Lavage Fluid, Lung
Abstract

IL-9 is a Th2 cytokine that exerts pleiotropic activities, and might be involved in the regulation of lung inflammatory processes. To characterize the activity of IL-9 on lung injury, we compared the pulmonary responses to bleomycin (blm) in IL-9 transgenic (Tg5) and wild-type (FVB) mice. Following intratracheal instillation of lethal doses of blm, the mortality rate was markedly reduced in Tg5 mice compared to their wild-type counterparts (ie, 25% mortality for Tg5 versus 85% for FVB mice, 21 days after instillation of 0.05U blm/mouse). Histological and biochemical analyses showed that blm induced less lung injury and less epithelial damage in Tg5 as compared to FVB animals. This protection of Tg5 mice was accompanied by an expansion of eosinophils and B cells in the lungs. In addition, TGF-beta and prostaglandin-E2 (PGE2) levels in broncho-alveolar lavage fluid were also increased in transgenic mice. The contribution of B cells and eosinophils to the protective mechanism did not appear essential since eosinophil-deficient (IL-5 KO) and B-deficient (muMT) mice overexpressing IL-9 were also resistant to high doses of blm. We could rule out that TGF-beta was a key factor in the protective effect of IL-9 by blocking this mediator with neutralizing antibodies. Indomethacin treatment, which inhibited PGE2 production in both strains, suppressed the protection in Tg5 mice, supporting the idea that IL-9 controls blm-induced lung injury through a prostaglandin-dependent mechanism.

Published
2005

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