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The microbiota regulates type 2 immunity through RORγt + T cells
Abstract
Gut microbes make T cells keep the peace: Our guts harbor trillions of microbial inhabitants, some of which regulate the types of immune cells that are present in the gut. For instance, Clostridium species of bacteria induce a type of T cell that promotes tolerance between the host and its microbial contents. Ohnmacht et al. and Sefik et al. characterized a population of gut regulatory T cells in mice, which required gut microbiota to survive. Multiple bacterial species of the microbiota could induce transcription factor–expressing regulatory T cells that helped maintain immune homeostasis. Mice engineered to lack these transcription factors exhibited enhanced susceptibility to colonic inflammation and had elevated amounts of proinflammatory molecules associated with allergies (see the Perspective by Hegazy and Powrie). Science , this issue pp. 989 and 993
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“Yet, Helios, Nrp-1 or ROR-γt are widely accepted for the discrimination of tTreg and pTreg cells under homeostatic conditions [364-366, 437-440].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [438]
In the citing paper
“In addition, the gut microbiome regulates the activity of retinoic acid receptor-related orphan receptor gamma-positive (RORγ+) Treg cells, dysregulation of which can lead to diseases such as colitis, food allergy, and colon cancer.622,701–704”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [703]
In the citing paper
“Significantly reduced RORγt+ Tregs in GF or antibiotic-treated mice promote Th2 type-associated immune responses and inflammation upon helminth infection.134”
From Interaction between microbiota and immunity in health and disease (2020) · cites this paper as [134]
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Cites
Bettelli, E., Carrier, Y., Gao, W., Korn, T., Strom, T. B., Oukka, M., Weiner, H. L., & Kuchroo, V. K. (2006) · Nature · doi:10.1038/nature04753 · Cited by 6,992
Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells
Furusawa, Y., Obata, Y., Fukuda, S., Endo, T. A., Nakato, G., Takahashi, D., Nakanishi, Y., Uetake, C., Kato, K., Kato, T., et al. (2013) · Nature · doi:10.1038/nature12721 · Cited by 5,549
Self-citationThe Microbial Metabolites, Short-Chain Fatty Acids, Regulate Colonic T reg Cell Homeostasis
Smith, P. M., Howitt, M. R., Panikov, N., Michaud, M., Gallini, C. A., Bohlooly-Y, M., Glickman, J. N., & Garrett, W. S. (2013) · Science · doi:10.1126/science.1241165 · Cited by 5,413
Ivanov, I. I., McKenzie, B. S., Zhou, L., Tadokoro, C. E., Lepelley, A., Lafaille, J. J., Cua, D. J., & Littman, D. R. (2006) · Cell · doi:10.1016/j.cell.2006.07.035 · Cited by 5,145
Induction of Intestinal Th17 Cells by Segmented Filamentous Bacteria
Ivanov, I. I., Atarashi, K., Manel, N., Brodie, E. L., Shima, T., Karaoz, U., Wei, D., Goldfarb, K. C., Santee, C. A., Lynch, S. V., et al. (2009) · Cell · doi:10.1016/j.cell.2009.09.033 · Cited by 4,554
Self-citationCellular and molecular mechanisms of fibrosis
Wynn, T. (2008) · The Journal of Pathology · doi:10.1002/path.2277 · Cited by 4,495
Interleukin-10-deficient mice develop chronic enterocolitis
Kühn, R., Löhler, J., Rennick, D. M., Rajewsky, K., & Müller, W. (1993) · Cell · doi:10.1016/0092-8674(93)80068-p · Cited by 4,248
IL-23 drives a pathogenic T cell population that induces autoimmune inflammation
Langrish, C. L., Chen, Y., Blumenschein, W. M., Mattson, J., Basham, B., Sedgwick, J. D., McClanahan, T., Kastelein, R. A., & Cua, D. J. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20041257 · Cited by 4,099
Induction of Colonic Regulatory T Cells by Indigenous Clostridium Species
Atarashi, K., Tanoue, T., Shima, T., Imaoka, A., Kuwahara, T., Momose, Y., Cheng, G., Yamasaki, S., Saito, T., Ohba, Y., et al. (2011) · Science · doi:10.1126/science.1198469 · Cited by 3,752
Self-citationCTLA-4 Control over Foxp3 + Regulatory T Cell Function
Wing, K., Onishi, Y., Prieto-Martin, P., Yamaguchi, T., Miyara, M., Fehervari, Z., Nomura, T., & Sakaguchi, S. (2008) · Science · doi:10.1126/science.1160062 · Cited by 2,956
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Interaction between microbiota and immunity in health and disease
Zheng, D., Liwinski, T., & Elinav, E. (2020) · Cell Research · doi:10.1038/s41422-020-0332-7 · Cited by 3,947
The microbiota in adaptive immune homeostasis and disease
Honda, K., & Littman, D. R. (2016) · Nature · doi:10.1038/nature18848 · Cited by 1,846
Self-citationHomeostatic Immunity and the Microbiota
Belkaid, Y., & Harrison, O. J. (2017) · Immunity · doi:10.1016/j.immuni.2017.04.008 · Cited by 1,261
“Notably, peripherally-induced Treg cells are reduced under germ free conditions (Geuking et al., 2011; Ohnmacht et al., 2015; Sefik et al., 2015; Yang et al., 2016).”
InfluentialPathophysiology of Inflammatory Bowel Diseases
Chang, J. T. (2020) · New England Journal of Medicine · doi:10.1056/nejmra2002697 · Cited by 1,295
Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01743-1 · Cited by 1,193
Regulatory T Cells and Human Disease
Sakaguchi, S., Mikami, N., Wing, J. B., Tanaka, A., Ichiyama, K., & Ohkura, N. (2020) · Annual Review of Immunology · doi:10.1146/annurev-immunol-042718-041717 · Cited by 1,163
“In contrast, RORγt+Helios− Tregs are pTregs induced by the presence of intestinal microbiota, and the loss of RORγt expression by Tregs results in severe intestinal inflammation (86, 87).”
BackgroundSelf-citationMicrobial bile acid metabolites modulate gut RORγ+ regulatory T cell homeostasis
Song, X., Sun, X., Oh, S. F., Wu, M., Zhang, Y., Zheng, W., Geva-Zatorsky, N., Jupp, R., Mathis, D., Benoist, C., et al. (2020) · Nature · doi:10.1038/s41586-019-1865-0 · Cited by 1,024
Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)
Cossarizza, A., Chang, H., Radbruch, A., Acs, A., Adam, D., Adam‐Klages, S., Agace, W. W., Aghaeepour, N., Akdiş, M., Allez, M., et al. (2019) · European Journal of Immunology · doi:10.1002/eji.201970107 · Cited by 1,007
The gut microbiome: Relationships with disease and opportunities for therapy
Durack, J., & Lynch, S. V. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20180448 · Cited by 979
“Additionally, GF animals possess fewer T reg cells (Atarashi et al., 2011; Ohnmacht et al., 2015), lack regulatory gut CD4+CD8αα+ double-positive intra-epithelial lymphocytes (Cervantes-Barragan et al., 2017), have compromised innate lymphoid cell function (Hepworth et al., 2013), and are more…”
BackgroundBacterial metabolism of bile acids promotes generation of peripheral regulatory T cells
Campbell, C., McKenney, P. T., Konstantinovsky, D., Isaeva, O. I., Schizas, M., Verter, J., Mai, C., Jin, W.-B., Guo, C.-J., Violante, S., et al. (2020) · Nature · doi:10.1038/s41586-020-2193-0 · Cited by 901
Host–microbiota interactions in inflammatory bowel disease
Caruso, R., Lo, B. C., & Núñez, G. (2020) · Nature reviews. Immunology · doi:10.1038/s41577-019-0268-7 · Cited by 808
Impact of Omega-3 Fatty Acids on the Gut Microbiota
Costantini, L., Molinari, R., Farinon, B., & Merendino, N. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18122645 · Cited by 741
“Early exposure to microbes in the intestine could be a critical factor modulating the original Th2-biased immune response, to subsequently induce the differentiation of other Th cell lineages, such as Th1, Th17, and Treg cells [31].”
BackgroundHuman FOXP3+ Regulatory T Cell Heterogeneity and Function in Autoimmunity and Cancer
Wing, J. B., Tanaka, A., & Sakaguchi, S. (2019) · Immunity · doi:10.1016/j.immuni.2019.01.020 · Cited by 726
Self-citationRegulatory T cells in autoimmune disease
Dominguez-Villar, M., & Hafler, D. A. (2018) · Nature Immunology · doi:10.1038/s41590-018-0120-4 · Cited by 713
A weaning reaction to microbiota is required for resistance to immunopathologies in the adult
Al Nabhani, Z., Dulauroy, S., Marques, R., Cousu, C., Al Bounny, S., Déjardin, F., Sparwasser, T., Bérard, M., Cerf-Bensussan, N., & Eberl, G. (2019) · Immunity · doi:10.1016/j.immuni.2019.02.014 · Cited by 679
Kennedy, E. A., King, K. Y., & Baldridge, M. T. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01534 · Cited by 602
The Gut Microbiota in Inflammatory Bowel Disease
Qiu, P., Ishimoto, T., Fu, L., Zhang, J., Zhang, Z., & Liu, Y. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.733992 · Cited by 654
“colonization promoted the aggregation of RORg T +FOXP3T+pTreg cells, which, conversely, resulted in inhibiting the response of colonic Th2 and Th17 cells (Ohnmacht et al., 2015).”
BackgroundCytokine Regulation and Function in T Cells
Dong, C. (2021) · Annual Review of Immunology · doi:10.1146/annurev-immunol-061020-053702 · Cited by 625
Britton, G. J., Contijoch, E. J., Mogno, I., Vennaro, O. H., Llewellyn, S. R., Ng, R., Li, Z., Mortha, A., Merad, M., Das, A., et al. (2019) · Immunity · doi:10.1016/j.immuni.2018.12.015 · Cited by 549
Development and maintenance of intestinal regulatory T cells
Tanoue, T., Atarashi, K., & Honda, K. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2016.36 · Cited by 553
Self-citationRegulation of the host immune system by helminth parasites
Maizels, R. M., & McSorley, H. J. (2016) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2016.07.007 · Cited by 585
Single-Cell Transcriptomics of Regulatory T Cells Reveals Trajectories of Tissue Adaptation
Miragaia, R. J., Gomes, T., Chomka, A., Jardine, L., Riedel, A., Hegazy, A. N., Whibley, N., Tucci, A., Chen, X., Lindeman, I., et al. (2019) · Immunity · doi:10.1016/j.immuni.2019.01.001 · Cited by 499
“…the homogeneity of colonic Tregs, with no differentially expressed genes detected between putative subclusters, in contrast to previous reports of phenotypically and functionally diverse subpopulations of CD4+ T cells within NLTs (Ohnmacht et al. 2015; Schiering et al. 2014; Sefik et al. 2015).”
ResultDietary antigens limit mucosal immunity by inducing regulatory T cells in the small intestine
Kim, K. S., Hong, S., Han, D., Yi, J., Jung, J., Yang, B., Lee, J. Y., Lee, M., & Surh, C. D. (2016) · Science · doi:10.1126/science.aac5560 · Cited by 541
“Collectively, these findings extend the recent reports (18, 19) by showing that while RORγt pTreg cells are induced by commensal microbiota, RORγt pTreg cells are driven by dietary Ags.”
ResultPanduro, M., Benoist, C., & Mathis, D. (2016) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032712-095948 · Cited by 536
“VAT Tregs are clearly tTregs, as argued by their TCR repertoire (27); their high expression of Helios and Nrp-1 (31) (markers of thymically differentiated Tregs) (124, 125); the lack of any transcriptomic sign of Tconv→Treg cell conversion (31); and the failure of transfer experiments to evidence them (31).”
BackgroundInfluentialGuidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)
Cossarizza, A., Chang, H., Radbruch, A., Abrignani, S., Addo, R., Akdis, M., Andrä, I., Andreata, F., Annunziato, F., Arranz, E., et al. (2021) · European Journal of Immunology · doi:10.1002/eji.202170126 · Cited by 531
He, B., Nohara, K., Park, N., Park, Y.-S., Guillory, B., Zhao, Z., Garcia, J. M., Koike, N., Lee, C. C., Takahashi, J. S., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.03.007 · Cited by 511
“Recent studies also showed that RORg deficiency compromises immunity to pathogens and parasites (Ohnmacht et al., 2015; Okada et al., 2015).”
Backgroundc-MAF-dependent regulatory T cells mediate immunological tolerance to a gut pathobiont
Xu, M., Pokrovskii, M., Ding, Y., Yi, R., Au, C., Harrison, O. J., Galan, C., Belkaid, Y., Bonneau, R., & Littman, D. R. (2018) · Nature · doi:10.1038/nature25500 · Cited by 498
Saravia, J., Chapman, N. M., & Chi, H. (2019) · Cellular & Molecular Immunology · doi:10.1038/s41423-019-0220-6 · Cited by 489
Principles of regulatory T cell function
Dikiy, S., & Rudensky, A. Y. (2023) · Immunity · doi:10.1016/j.immuni.2023.01.004 · Cited by 470
Induced Regulatory T Cells: Their Development, Stability, and Applications
Kanamori, M., Nakatsukasa, H., Okada, M., Lu, Q., & Yoshimura, A. (2016) · Trends in Immunology · doi:10.1016/j.it.2016.08.012 · Cited by 465
Tan, T. G., Sefik, E., Geva-Zatorsky, N., Kua, L., Naskar, D., Teng, F., Pasman, L., Ortiz-Lopez, A., Jupp, R., Wu, H.-J. J., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1617460113 · Cited by 427
CD4 + T-cell subsets in inflammatory diseases: beyond the T h 1/T h 2 paradigm
Hirahara, K., & Nakayama, T. (2016) · International Immunology · doi:10.1093/intimm/dxw006 · Cited by 417
Single-cell gene expression reveals a landscape of regulatory T cell phenotypes shaped by the TCR
Zemmour, D., Zilionis, R., Kiner, E., Klein, A. M., Mathis, D., & Benoist, C. (2018) · Nature Immunology · doi:10.1038/s41590-018-0051-0 · Cited by 384
“This confluence is reminiscent of the earlier reports that TFs characteristic of terminally differentiated T conv states have also a critical role in T reg suppression (Tbx21, Rorc, Bcl6) 7,10,72–75 .”
The immunology of the allergy epidemic and the hygiene hypothesis
Lambrecht, B. N., & Hammad, H. (2017) · Nature Immunology · doi:10.1038/ni.3829 · Cited by 424
Cervical Microbiome and Cytokine Profile at Various Stages of Cervical Cancer: A Pilot Study
Audirac-Chalifour, A., Torres-Poveda, K., Bahena-Román, M., Téllez‐Sosa, J., Martínez-Barnetche, J., Cortina-Ceballos, B., López-Estrada, G., Delgado-Romero, K., Burguete-García, A. I., de León, D. F. C., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0153274 · Cited by 416
“Likewise, it was demonstrated in a recent study that the microbiota regulates Th2 immunity through the induction of type 3 RORγτ+ Tregs and Th17, acting as a key element to balance the immune responses of the epithelial cells [74].”
BackgroundStability and function of regulatory T cells expressing the transcription factor T-bet
Levine, A. G., Mendoza, A., Hemmers, S., Moltedo, B., Niec, R. E., Schizas, M., Hoyos, B. E., Putintseva, E. V., Chaudhry, A., Dikiy, S., et al. (2017) · Nature · doi:10.1038/nature22360 · Cited by 394
Gonçalves, P., Araújo, J. R., & Santo, J. P. D. (2018) · Inflammatory Bowel Diseases · doi:10.1093/ibd/izx029 · Cited by 404
Microbiota therapy acts via a regulatory T cell MyD88/RORγt pathway to suppress food allergy
Abdel-Gadir, A., Victor, E. S., Gerber, G. K., Rivas, M. N., Wang, S., Harb, H., Wang, L., Li, N., Crestani, E., Spielman, S. C., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0461-z · Cited by 397
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Rivas, M. N., & Chatila, T. A. (2016) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2016.06.003 · Cited by 387
CD4 T Helper Cell Subsets and Related Human Immunological Disorders
Zhu, X., & Zhu, J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21218011 · Cited by 413
Thomas, S., Izard, J., Walsh, E. K., Batich, K. A., Chongsathidkiet, P., Clarke, G. A., Sela, D. A., Muller, A. J., Mullin, J. M., Albert, K., et al. (2017) · Cancer Research · doi:10.1158/0008-5472.can-16-2929 · Cited by 400
Donald, K., & Finlay, B. B. (2023) · Nature reviews. Immunology · doi:10.1038/s41577-023-00874-w · Cited by 394
T Helper Cell Differentiation, Heterogeneity, and PlasticityPreprint
Zhu, J. (2017) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a030338 · Cited by 374
“Interestingly, RORγt/Foxp3-coexpressing Treg cells, possibly representing a specialized Treg subset, are abundant in the large intestine (Ohnmacht et al. 2015; Sefik et al. 2015).”
BackgroundTordesillas, L., Berin, M. C., & Sampson, H. A. (2017) · Immunity · doi:10.1016/j.immuni.2017.07.004 · Cited by 346
Savage, P. A., Klawon, D. E. J., & Miller, C. H. (2020) · Annual Review of Immunology · doi:10.1146/annurev-immunol-100219-020937 · Cited by 321
Pathogenesis of ankylosing spondylitis — recent advances and future directions
Ranganathan, V., Gracey, E., Brown, M. A., Inman, R. D., & Haroon, N. (2017) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2017.56 · Cited by 317
Mining the microbiota for microbial and metabolite-based immunotherapies
Skelly, A. N., Sato, Y., Kearney, S., & Honda, K. (2019) · Nature Reviews Immunology · doi:10.1038/s41577-019-0144-5 · Cited by 306
Self-citationImprinting of the immune system by the microbiota early in life
Al Nabhani, Z., & Eberl, G. (2020) · Mucosal Immunology · doi:10.1038/s41385-020-0257-y · Cited by 301
Self-citationControl of Immunity by the Microbiota
Ansaldo, E., Farley, T. K., & Belkaid, Y. (2021) · Annual Review of Immunology · doi:10.1146/annurev-immunol-093019-112348 · Cited by 312
Bridging intestinal immunity and gut microbiota by metabolites
Wang, G., Huang, S., Wang, Y., Cai, S., Yu, H., Liu, H., Zeng, X., Zhang, G., & Qiao, S. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03190-6 · Cited by 305
ILC3s select microbiota-specific regulatory T cells to establish tolerance in the gut
Lyu, M., Suzuki, H., Kang, L., Gaspal, F., Zhou, W., Goc, J., Zhou, L., Zhou, J., Zhang, W., Bank, J. L. C., et al. (2022) · Nature · doi:10.1038/s41586-022-05141-x · Cited by 304
Self-citationLuna, R. A., Oezguen, N., Balderas, M., Venkatachalam, A., Runge, J. K., Versalovic, J., Veenstra-VanderWeele, J., Anderson, G. M., Savidge, T., & Williams, K. C. (2017) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2016.11.008 · Cited by 295
Novel antigen-presenting cell imparts Treg-dependent tolerance to gut microbiota
Akagbosu, B., Tayyebi, Z., Shibu, G., Paucar Iza, Y. A., Deep, D., Parisotto, Y. F., Fisher, L., Pasolli, H. A., Thevin, V., Elmentaite, R., et al. (2022) · Nature · doi:10.1038/s41586-022-05309-5 · Cited by 273
Microbial antigen encounter during a preweaning interval is critical for tolerance to gut bacteria
Knoop, K. A., Gustafsson, J. K., McDonald, K. G., Kulkarni, D. H., Coughlin, P. E., McCrate, S., Kim, D., Hsieh, C., Hogan, S. P., Elson, C. O., et al. (2017) · Science Immunology · doi:10.1126/sciimmunol.aao1314 · Cited by 270
Interplay between diet, gut microbiota, epigenetic events, and colorectal cancer
Bultman, S. J. (2016) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201500902 · Cited by 275
Th17 plasticity and its relevance to inflammatory bowel disease
Ueno, A., Jeffery, L. E., Kobayashi, T., Hibi∥, T., Ghosh, S. K., & Jijon, H. B. (2017) · Journal of Autoimmunity · doi:10.1016/j.jaut.2017.12.004 · Cited by 273
The impact of gut microbiota on gender-specific differences in immunity
Fransen, F., van Beek, A. A., Borghuis, T., Meijer, B., Hugenholtz, F., van der Gaast-de Jongh, C., Savelkoul, H. F., de Jonge, M. I., Faas, M. M., Boekschoten, M. V., et al. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00754 · Cited by 266
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BackgroundEmerging Functions of Regulatory T Cells in Tissue Homeostasis
Sharma, A., & Rudra, D. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00883 · Cited by 273
Tordesillas, L., & Berin, M. C. (2018) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-018-8680-5 · Cited by 276
Antibiotics in early life: dysbiosis and the damage done
Neuman, H., Forsythe, P., Uzan-Yulzari, A., Avni, O., & Koren, O. (2018) · FEMS Microbiology Reviews · doi:10.1093/femsre/fuy018 · Cited by 271
“…phenotype that involves maturation of the Th1 and Th17 cells response and the development of T regulatory (Treg) cells, which suppress the Th2-phenotype (Alexander, Targan and Elson 2014; Faith et al. 2014; Ohnmacht et al. 2015; Sefik et al. 2015; Tan et al. 2016; Zhang, Zhivaki and Lo-Man 2017).”
BackgroundZhang, Z., Tang, H., Chen, P., Xie, H., & Tao, Y. (2019) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-019-0074-5 · Cited by 263
Tissue adaptation of regulatory and intraepithelial CD4 + T cells controls gut inflammation
Sujino, T., London, M., Hoytema van Konijnenburg, D. P., Rendon, T., Buch, T., Silva, H. M., Lafaille, J. J., Reis, B. S., & Mucida, D. (2016) · Science · doi:10.1126/science.aaf3892 · Cited by 250
Yissachar, N., Zhou, Y., Ung, L., Lai, N. Y., Mohan, J. F., Ehrlicher, A., Weitz, D. A., Kasper, D. L., Chiu, I. M., Mathis, D., et al. (2017) · Cell · doi:10.1016/j.cell.2017.02.009 · Cited by 242
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BackgroundInfluentialCD4 T-Cell Subsets and the Pathophysiology of Inflammatory Bowel Disease
Gómez-Bris, R., Saéz, Á., Herrero‐Fernández, B., Rius, C., Sánchez-Martinez, H., & González, J. M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032696 · Cited by 265
Crosstalk between Gut Microbiota and Host Immunity: Impact on Inflammation and Immunotherapy
Campbell, C., Kandalgaonkar, M. R., Golonka, R. M., Yeoh, B. S., Vijay–Kumar, M., & Saha, P. (2023) · Biomedicines · doi:10.3390/biomedicines11020294 · Cited by 270
Reber, S. O., Siebler, P. H., Donner, N. C., Morton, J. T., Smith, D. G., Kopelman, J. M., Lowe, K. R., Wheeler, K. J., Fox, J. H., Hassell, J. E., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1600324113 · Cited by 233
Verma, R., Lee, C., Jeun, E.-J., Yi, J., Kim, K. S., Ghosh, A., Byun, S., Lee, C.-G., Kang, H.-J., Kim, G.-C., et al. (2018) · Science Immunology · doi:10.1126/sciimmunol.aat6975 · Cited by 242
Regulatory T Cells: the Many Faces of Foxp3
Georgiev, P., Charbonnier, L., & Chatila, T. A. (2019) · Journal of Clinical Immunology · doi:10.1007/s10875-019-00684-7 · Cited by 253
Cantorna, M. T., Snyder, L. M., & Arora, J. (2019) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2019.1611734 · Cited by 244
“In addition, there is a population of microbiota specific FoxP3/Rorctþ expressing T regulatory (reg) cells in the colon lamina propria (LP) that require the microbiota (Ohnmacht et al. 2015).”
BackgroundVemuri, R., Sylvia, K. E., Klein, S. L., Forster, S. C., Plebanski, M., Eri, R., & Flanagan, K. L. (2019) · Seminars in Immunopathology · doi:10.1007/s00281-018-0716-7 · Cited by 265
Microbiome Dependent Regulation of Tregs and Th17 Cells in Mucosa
Pandiyan, P., Bhaskaran, N., Zou, M., Schneider, E., Jayaraman, S., & Huehn, J. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00426 · Cited by 237
The microbiome and autoimmunity: a paradigm from the gut–liver axis
Li, B., Selmi, C. F., Tang, R., Gershwin, M. E., & Ma, X. (2018) · Cellular and Molecular Immunology · doi:10.1038/cmi.2018.7 · Cited by 237
Modulation of T cells by tryptophan metabolites in the kynurenine pathway
Stone, T. W., & Williams, R. O. (2023) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2023.04.006 · Cited by 233
Konkel, J. E., Zhang, D., Zanvit, P., Chia, C., Zangerle-Murray, T., Jin, W., Wang, S., & Chen, W. (2017) · Immunity · doi:10.1016/j.immuni.2017.03.015 · Cited by 231
Reynolds, L. A., Finlay, B. B., & Maizels, R. M. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1501432 · Cited by 226
Parasite-Microbiota Interactions With the Vertebrate Gut: Synthesis Through an Ecological Lens
Leung, J. M., Graham, A. L., & Knowles, S. C. L. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.00843 · Cited by 225
“Ohnmacht et al. (2015) demonstrated that mice lacking microbiota-inducible RORγt+ Tregs had stronger Th2 immunity and hence greater resistance to H. polygyrus infection, implying that Treg induction by the microbiota ordinarily promotes H. polygyrus persistence (Ohnmacht et al., 2015).”
BackgroundFood allergy and the microbiome: Current understandings and future directions
Bunyavanich, S., & Berin, M. C. (2019) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2019.10.019 · Cited by 225
The microbiome in posttraumatic stress disorder and trauma-exposed controls: an exploratory study
Hemmings, S. M. J., Malan-Müller, S., van den Heuvel, L. L., Demmitt, B. A., Stanislawski, M. A., Smith, D. G., Bohr, A. D., Stamper, C. E., Hyde, E. R., Morton, J. T., et al. (2017) · Psychosomatic Medicine · doi:10.1097/psy.0000000000000512 · Cited by 208
IgE and IgG Antibodies as Regulators of Mast Cell and Basophil Functions in Food Allergy
Kanagaratham, C., Ansari, Y. S. E., Lewis, O. L., & Oettgen, H. C. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.603050 · Cited by 214
Metabolic Control of Treg Cell Stability, Plasticity, and Tissue-Specific Heterogeneity
Shi, H., & Chi, H. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02716 · Cited by 211
Holobionts as Units of Selection and a Model of Their Population Dynamics and Evolution
Roughgarden, J. E., Gilbert, S. F., ROSENBERG, E. B., Zilber‐Rosenberg, I., & Lloyd, E. A. (2017) · Biological Theory · doi:10.1007/s13752-017-0287-1 · Cited by 206
“2013) as well as for inducing the specific lymphocyte populations that balance the immune response at mucosal surfaces (Ohnmacht et al. 2015).”
BackgroundImmunology of Inflammatory Bowel Disease: Molecular Mechanisms and Therapeutics
Lu, Q., Yang, M.-F., Liang, Y.-J., Xu, J., Xu, H.-M., Nie, Y.-Q., Wang, L.-S., Yao, J., & Li, D.-F. (2022) · Journal of Inflammation Research · doi:10.2147/jir.s353038 · Cited by 222
Takahashi, D., Hoshina, N., Kabumoto, Y., Maeda, Y., Suzuki, A., Tanabe, H., Isobe, J., Yamada, T., Muroi, K., Yanagisawa, Y., et al. (2020) · EBioMedicine · doi:10.1016/j.ebiom.2020.102913 · Cited by 205
Self-citationAllergy associations with the adult fecal microbiota: Analysis of the American Gut Project
Hua, X., Goedert, J. J., Pu, A., Yu, G., & Shi, J. (2015) · EBioMedicine · doi:10.1016/j.ebiom.2015.11.038 · Cited by 207
“More recently, Ohnmacht et al. demonstrated in mice that the microbial population of the gut (the microbiota) controls systemic Th2 responses by inducing enteric Th17 and regulatory T cells (Ohnmacht et al., 2015).”
BackgroundBradley, C. P., Teng, F., Felix, K. M., Sano, T., Naskar, D., Block, K. E., Huang, H., Knox, K. S., Littman, D. R., & Wu, H.-J. J. (2017) · Cell Host & Microbe · doi:10.1016/j.chom.2017.10.007 · Cited by 204
“A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript expresses Rorγt in addition to Foxp3 and displays an anti-inflammatory effect in colitis models (Sefik et al., 2015; Ohnmacht et al., 2015).”
BackgroundChapman, N. M., Zeng, H., Nguyen, T.-L. M., Wang, Y., Vogel, P., Dhungana, Y., Liu, X., Neale, G. A. M., Locasale, J. W., & Chi, H. (2018) · Nature Communications · doi:10.1038/s41467-018-04392-5 · Cited by 194
Eberl, G. (2016) · Nature reviews. Immunology · doi:10.1038/nri.2016.75 · Cited by 200
Self-citationNeonatal gut microbiome and immunity
Sanidad, K. Z., & Zeng, M. Y. (2020) · Current Opinion in Microbiology · doi:10.1016/j.mib.2020.05.011 · Cited by 205
Targeting the gut‐skin axis—Probiotics as new tools for skin disorder management?
Szántó, M., Dózsa, A., Antal, D., Szabó, K., Kemény, L., & Bai, P. (2019) · Experimental Dermatology · doi:10.1111/exd.14016 · Cited by 189
Regionalized Development and Maintenance of the Intestinal Adaptive Immune Landscape
Agace, W. W., & McCoy, K. D. (2017) · Immunity · doi:10.1016/j.immuni.2017.04.004 · Cited by 194
“…degrees (Sefik et al., 2015); a dominant species possessing such activity in both humans and mice appears to be the Clostridia that promote mucosal TGFb production and RORgt+FoxP3+ pTreg cell generation independently of MyD88 (Atarashi et al., 2013; Atarashi et al., 2011; Ohnmacht et al., 2015).”
BackgroundInfluentialFood Allergy and Intolerance: A Narrative Review on Nutritional Concerns
Gargano, D., Appanna, R., Santonicola, A., Bartolomeis, F. D., Stellato, C., Cianferoni, A., Casolaro, V., & Iovino, P. (2021) · Nutrients · doi:10.3390/nu13051638 · Cited by 207
“Studies in germ-free mice demonstrated that microbiota-delivered factors can regulate Th2-driven immunity through the induction of Th17 cells and of a subset of Treg cells expressing the Th17 signature factor, retinoid-related orphan receptor (ROR)-γt [137].”
BackgroundProfound Treg perturbations correlate with COVID-19 severity
Galván-Peña, S., Léon, J., Chowdhary, K., Michelson, D. A., Vijaykumar, B., Yang, L., Magnuson, A. M., Chen, F., Manickas-Hill, Z., Trocha, A. K., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2111315118 · Cited by 189
“More recent studies have painted a more nuanced picture of IL-6 in relation to Treg cells: it is required for the differentiation of the ROR γ + Treg subpopulation (41, 42) and can increase their suppressive capabilities (43).”
Wang, B., Zhang, L., Wang, Y., Dai, T., Qin, Z., Zhou, F., & Zhang, L. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00986-0 · Cited by 187
The effects of early life adversity on the immune system
Elwenspoek, M. M. C., Kuehn, A., Muller, C. P., & Turner, J. D. (2017) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.05.012 · Cited by 191
“Regulatory T cells (Treg) expressing FoxP3 prevent allergic inflammation and regulate the Th2 response (Ohnmacht et al., 2015; Vock et al., 2010), particularly by suppressing Th1, Th2, and Th17 cell migration (Akdis and Akdis, 2009).”
Neumann, C., Blume, J., Roy, U., Teh, P. P., Vasanthakumar, A., Beller, A. V., Liao, Y., Heinrich, F., Arenzana, T. L., Hackney, J. A., et al. (2019) · Nature Immunology · doi:10.1038/s41590-019-0316-2 · Cited by 179
Critical role of the gut microbiota in immune responses and cancer immunotherapy
Li, Z., Xiong, W., Zhu, L. W., Wang, J., Zeng, Z., Kołat, D., Li, X., Zhou, D., Xu, X., & Zhao, L.-Y. (2024) · Journal of Hematology & Oncology · doi:10.1186/s13045-024-01541-w · Cited by 197
The Aryl Hydrocarbon Receptor Preferentially Marks and Promotes Gut Regulatory T Cells
Ye, J., Qiu, J., Bostick, J. W., Ueda, A., Schjerven, H., Li, S., Jobin, C., Chen, Z. E., & Zhou, L. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.10.114 · Cited by 183
“…of splenic Ahr-deficient Tregs in suppressing T cell transfer-mediated colitis was observed, consistent with the more suppressive function of RORgt+ Tregs and/or activated Tregs in various animal models of disease (Kim et al., 2016; Luo et al., 2016; Ohnmacht et al., 2015; Sefik et al., 2015).”
ResultKimura, T., Kobiyama, K., Winkels, H., Tse, K. Y., Miller, J. F., Vassallo, M., Wolf, D., Ryden, C., Orecchioni, M., Dileepan, T., et al. (2018) · Circulation · doi:10.1161/circulationaha.117.031420 · Cited by 178
An Immunologic Mode of Multigenerational Transmission Governs a Gut Treg Setpoint
Ramanan, D., Sefik, E., Galván-Peña, S., Wu, M., Yang, L., Yang, Z., Kostic, A. D., Golovkina, T. V., Kasper, D. L., Mathis, D. J., et al. (2020) · Cell · doi:10.1016/j.cell.2020.04.030 · Cited by 179
Fang, D., & Zhu, J. (2017) · Journal of Experimental Medicine · doi:10.1084/jem.20170494 · Cited by 175
“Two recent studies indicated that RORγt/Foxp3-coexpressing cells, highly enriched in the large intestine, may represent a subset of Treg cells (Ohnmacht et al., 2015; Sefik et al., 2015).”
Background
Metadata
- Authors
- Ohnmacht, C., Park, J.-H., Cording, S., Wing, J. B., Atarashi, K., Obata, Y., Gaboriau-Routhiau, V., Marques, R., Dulauroy, S., Fedoseeva, M., Busslinger, M., Cerf-Bensussan, N., Boneca, I. G., Voehringer, D., Hase, K., Honda, K., Sakaguchi, S., & Eberl, G.
- Affiliations
- Institut Pasteur (FR)
- Immunology Frontier Research Center, The University of Osaka (JP)
- Japan Science and Technology Agency (JP)
- Institute of Medical Science, The University of Tokyo (JP)
- INSERM, U1163, Laboratory of Intestinal Immunity, Paris, France.
- Helmholtz Munich (DE)
- Research Institute of Molecular Pathology (AT)
- Inserm (FR)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Kyoto University (JP)
- Corresponding author
- Ohnmacht, Caspar
- Park, Joo-Hong
- Eberl, Gérard
- ORCID
- Venue
- Science
- Published
- 2015-08-28
- Volume
- 349
- Issue
- 6251
- Pages
- 989-993
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2126657409
- Cited by
- 863
- References
- 53
- Citations by year
- 2026: 55 · 2025: 84 · 2024: 59 · 2023: 86 · 2022: 88 · 2021: 96 · 2020: 87 · 2019: 87 · 2018: 78 · 2017: 68 · 2016: 65 · 2015: 10
- FWCI
- 36.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Site cant be reached (submittedVersion)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
- Funders
- Boehringer Ingelheim
- European Molecular Biology Organization
- European Commission (MEXT-CT-2006-042374)
- Agence Nationale de la Recherche (ANR 11 BSV3 020 01)
- Japan Society for the Promotion of Science (15K19129)
- Institut Pasteur
- Fondation de la Recherche Medicale (DEq. 2010318246)
- Fondation Simone e Cino Del Duca from the Institut de France
- Integrative Biology of Emerging Infectious Diseases (ANR-10-LABX-62-IBEID)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Keywords
- gut microbiota, Th2 immune response, RORγt, regulatory T cells, Th17 cells, Th2 cells, helminthiasis, allergic inflammation, mucosal immunity, nuclear receptors, intestinal immune regulation
- MeSH terms
- Animals, Colitis, Ulcerative, Colon, Germ-Free Life, Homeostasis, Intestinal Mucosa, Intestine, Small, Intestines, Nematospiroides dubius, Specific Pathogen-Free Organisms, Vitamin A, T-Lymphocyte Subsets, Strongylida Infections, Th2 Cells, Models, Immunological, Immunity, Mucosal, T-Lymphocytes, Regulatory, Mice, Nuclear Receptor Subfamily 1, Group F, Member 3, Th17 Cells, Microbiota
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