The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index.
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
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Citations
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
Self-citationThe Effect of Infections on Susceptibility to Autoimmune and Allergic Diseases
Bach, J. (2002) · New England Journal of Medicine · doi:10.1056/nejmra020100 · Cited by 2,723
Reciprocal T H 17 and Regulatory T Cell Differentiation Mediated by Retinoic Acid
Mucida, D., Park, Y., Kim, G., Turovskaya, O., Scott, I., Kronenberg, M., & Cheroutre, H. (2007) · Science · doi:10.1126/science.1145697 · Cited by 1,982
TGF-β-induced Foxp3 inhibits TH17 cell differentiation by antagonizing RORγt function
Zhou, L., Lopes, J. E., Chong, M. M. W., Ivanov, I. I., Min, R., Victora, G. D., Shen, Y., Du, J., Rubtsov, Y. P., Rudensky, A. Y., et al. (2008) · Nature · doi:10.1038/nature06878 · Cited by 1,928
IL-17 family cytokines and the expanding diversity of effector T cell lineages
Weaver, C. T., Hatton, R. D., Mangan, P. R., & Harrington, L. E. (2007) · Annual Review of Immunology · doi:10.1146/annurev.immunol.25.022106.141557 · Cited by 1,842
Ivanov, I. I., Frutos, R. D. L., Manel, N., Yoshinaga, K., Rifkin, D. B., Sartor, R. B., Finlay, B. B., & Littman, D. R. (2008) · Cell Host & Microbe · doi:10.1016/j.chom.2008.09.009 · Cited by 1,770
Impaired immune and acute-phase responses in interleukin-6-deficient mice
Kopf, M., Baumann, H., Freer, G., Freudenberg, M., Lamers, M., Kishimoto, T., Zinkernagel, R., Bluethmann, H., & Köhler, G. (1994) · Nature · doi:10.1038/368339a0 · Cited by 1,768 · cited 1×
“2 Materials and Methods Mice Foxp3 mice (43) were crossed to Rorc(γt) mice (15) and maintained on a C57BL/6 background, as were Cd11c x Rosa26 (ΔDC) mice (44), IL-2-deficient (45), IL-10deficient (46), IL-6-deficient (47), Il23a-deficient (48), Nod1/Nod2- and Myd88/Trifdouble deficient mice, Il10 (21) and Gata3 mice (…”
MethodMicrobial Exposure During Early Life Has Persistent Effects on Natural Killer T Cell Function
Olszak, T., An, D., Zeissig, S., Vera, M. P., Richter, J., Franke, A., Glickman, J. N., Siebert, R., Baron, R. M., Kasper, D. L., et al. (2012) · Science · doi:10.1126/science.1219328 · Cited by 1,661
Barnden, M., Allison, J., Heath, W. R., & Carbone, F. (1998) · Immunology and Cell Biology · doi:10.1046/j.1440-1711.1998.00709.x · Cited by 1,491
Gaboriau-Routhiau, V., Rakotobe, S., Lécuyer, E., Mulder, I., Lan, A., Bridonneau, C., Rochet, V., Pisi, A., De Paepe, M., Brandi, G., et al. (2009) · Immunity · doi:10.1016/j.immuni.2009.08.020 · Cited by 1,452
Self-citationThornton, A. M., Korty, P. E., Tran, D. Q., Wohlfert, E. A., Murray, P. E., Belkaid, Y., & Shevach, E. M. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0904028 · Cited by 1,382
Takeda, K., Clausen, B. E., Kaisho, T., Tsujimura, T., Terada, N., Förster, I., & Akira, S. (1999) · Immunity · doi:10.1016/s1074-7613(00)80005-9 · Cited by 1,220
Peripheral education of the immune system by colonic commensal microbiota
Lathrop, S. K., Bloom, S. M., Rao, S. M., Nutsch, K., Lio, C.-W., Santacruz, N., Peterson, D. A., Stappenbeck, T. S., & Hsieh, C.-S. (2011) · Nature · doi:10.1038/nature10434 · Cited by 1,034
The alarmin IL-33 promotes regulatory T-cell function in the intestine
Schiering, C., Krausgruber, T., Chomka, A., Fröhlich, A., Adelmann, K., Wohlfert, E. A., Pott, J., Griseri, T., Bollrath, J., Hegazy, A. N., et al. (2014) · Nature · doi:10.1038/nature13577 · Cited by 1,007
Eberl, G., Marmon, S., Sunshine, M. J., Rennert, P. D., Choi, Y., & Littman, D. R. (2003) · Nature Immunology · doi:10.1038/ni1022 · Cited by 986
Self-citationRegulatory T-cell suppressor program co-opts transcription factor IRF4 to control TH2 responses
Zheng, Y., Chaudhry, A., Kas, A., deRoos, P., Kim, J. M., Chu, T.-T., Corcoran, L., Treuting, P., Klein, U., & Rudensky, A. Y. (2009) · Nature · doi:10.1038/nature07674 · Cited by 958
Early life antibiotic‐driven changes in microbiota enhance susceptibility to allergic asthma
Russell, S. L., Gold, M. J., Hartmann, M., Willing, B. P., Thorson, L., Wlodarska, M., Gill, N., Blanchet, M., Mohn, W. W., McNagny, K. M., et al. (2012) · The EMBO Reports · doi:10.1038/embor.2012.32 · Cited by 883
Development and function of T cells in mice rendered interleukin-2 deficient by gene targeting
Schorle, H., Holtschke, T., Hünig, T., Schimpl, A., & Horak, I. D. (1991) · Nature · doi:10.1038/352621a0 · Cited by 877
Extrathymically generated regulatory T cells control mucosal TH2 inflammation
Josefowicz, S. Z., Niec, R. E., Kim, H. Y., Treuting, P. M., Chinen, T., Zheng, Y., Umetsu, D. T., & Rudensky, A. Y. (2012) · Nature · doi:10.1038/nature10772 · Cited by 862
IL-6 induces an anti-inflammatory response in the absence of SOCS3 in macrophages
Yasukawa, H., Ohishi, M., Mori, H., Murakami, M., Chinen, T., Aki, D., Hanada, T., Takeda, K., Akira, S., Hoshijima, M., et al. (2003) · Nature Immunology · doi:10.1038/ni938 · Cited by 771
Heller, F., Fuss, I., Nieuwenhuis, E., Blumberg, R., & Strober, W. (2002) · Immunity · doi:10.1016/s1074-7613(02)00453-3 · Cited by 648
Weiss, J. M., Bilate, A. M., Gobert, M., Ding, Y., Curotto de Lafaille, M. A., Parkhurst, C. N., Xiong, H., Dolpady, J., Frey, A. B., Ruocco, M. G., et al. (2012) · Journal of Experimental Medicine · doi:10.1084/jem.20120914 · Cited by 621
Intestinal Microbial Diversity during Early-Life Colonization Shapes Long-Term IgE Levels
Cahenzli, J., Köller, Y., Wyss, M., Geuking, M. B., & McCoy, K. D. (2013) · Cell Host & Microbe · doi:10.1016/j.chom.2013.10.004 · Cited by 611
Ohnmacht, C., Pullner, A., King, S. B. S., Drexler, I., Meier, S., Brocker, T., & Voehringer, D. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20082394 · Cited by 597
Self-citationSawa, S., Lochner, M., Satoh‐Takayama, N., Dulauroy, S., Berard, M., Kleinschek, M. A., Cua, D., Santo, J. P. D., & Eberl, G. (2011) · Nature Immunology · doi:10.1038/ni.2002 · Cited by 596
Self-citationIdentifying Foxp3-expressing suppressor T cells with a bicistronic reporter
Wan, Y. Y., & Flavell, R. A. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501701102 · Cited by 568
In vivo equilibrium of proinflammatory IL-17+ and regulatory IL-10+ Foxp3+ RORγt+ T cells
Lochner, M., Peduto, L., Cherrier, M., Sawa, S., Vives, F. L., Varona, R., Riethmacher, D., Si‐Tahar, M., Santo, J. P. D., & Eberl, G. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20080034 · Cited by 558
Self-citationGATA3 controls Foxp3+ regulatory T cell fate during inflammation in mice
Wohlfert, E. A., Grainger, J. R., Bouladoux, N., Konkel, J. E., Oldenhove, G., Ribeiro, C. H., Hall, J. A., Yagi, R., Naik, S., Bhairavabhotla, R., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci57456 · Cited by 556
Boirivant, M., Fuss, I. J., Chu, A., & Strober, W. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.188.10.1929 · Cited by 529
An enteric virus can replace the beneficial function of commensal bacteria
Kernbauer, E., Ding, Y., & Cadwell, K. (2014) · Nature · doi:10.1038/nature13960 · Cited by 527
Thymic Origin of Intestinal αß T Cells Revealed by Fate Mapping of RORγt + Cells
Eberl, G., & Littman, D. R. (2004) · Science · doi:10.1126/science.1096472 · Cited by 514
Self-citationCommensal bacteria-derived signals regulate basophil hematopoiesis and allergic inflammation
Hill, D. A., Siracusa, M. C., Abt, M. C., Kim, B. S., Kobuley, D., Kubo, M., Kambayashi, T., LaRosa, D. F., Renner, E. D., Orange, J. S., et al. (2012) · Nature Medicine · doi:10.1038/nm.2657 · Cited by 468
Transcription factor Foxp3 and its protein partners form a complex regulatory network
Rudra, D., DeRoos, P. C., Chaudhry, A., Niec, R. E., Arvey, A. J., Samstein, R. M., Leslie, C. S., Shaffer, S. A., Goodlett, D. R., & Rudensky, A. Y. (2012) · Nature Immunology · doi:10.1038/ni.2402 · Cited by 448
Adaptation of Innate Lymphoid Cells to a Micronutrient Deficiency Promotes Type 2 Barrier Immunity
Spencer, S. P., Wilhelm, C., Yang, Q., Hall, J. A., Bouladoux, N., Boyd, A., Nutman, T. B., Urban, J. F., Wang, J., Ramalingam, T. R., et al. (2014) · Science · doi:10.1126/science.1247606 · Cited by 447
Dysregulation of Allergic Airway Inflammation in the Absence of Microbial Colonization
Herbst, T., Sichelstiel, A., Schär, C., Yadava, K., Bürki, K., Cahenzli, J., McCoy, K., Marsland, B. J., & Harris, N. L. (2011) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201010-1574oc · Cited by 440
Toll-Like Receptor 4 Signaling by Intestinal Microbes Influences Susceptibility to Food Allergy
Bashir, M. E. H., Louie, S., Shi, H. N., & Nagler‐Anderson, C. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.11.6978 · Cited by 392
Maternal retinoids control type 3 innate lymphoid cells and set the offspring immunity
van de Pavert, S. A., Ferreira, M., Domingues, R. G., Ribeiro, H., Molenaar, R., Moreira-Santos, L., Almeida, F. F., Ibiza, S., Barbosa, I., Goverse, G., et al. (2014) · Nature · doi:10.1038/nature13158 · Cited by 374
Grote, D., Souabni, A., Busslinger, M., & Bouchard, M. (2005) · Development · doi:10.1242/dev.02184 · Cited by 351
Self-citationAllen, J. E., & Sutherland, T. E. (2014) · Seminars in Immunology · doi:10.1016/j.smim.2014.06.003 · Cited by 279
Yu, F., Sharma, S., Edwards, J., Feigenbaum, L., & Zhu, J. (2014) · Nature Immunology · doi:10.1038/ni.3053 · Cited by 253
Thakker, P., Leach, M. W., Kuang, W., Benoit, S., Leonard, J. P., & Marušić, S. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.4.2589 · Cited by 184
Natural IgE Production in the Absence of MHC Class II Cognate Help
McCoy, K. D., Harris, N. L., Diener, P., Hatak, S., Odermatt, B., Hangartner, L., Senn, B. M., Marsland, B. J., Geuking, M. B., Hengartner, H., et al. (2006) · Immunity · doi:10.1016/j.immuni.2006.01.013 · Cited by 124
Mucosal immunity and allergic responses: lack of regulation and/or lack of microbial stimulation?
Prioult, G., & Nagler‐Anderson, C. (2005) · Immunological Reviews · doi:10.1111/j.0105-2896.2005.00277.x · Cited by 121
Lochner, M., Berard, M., Sawa, S., Hauer, S., Gaboriau‐Routhiau, V., Fernández, T. D., Snel, J., Bousso, P., Cerf–Bensussan, N., & Eberl, G. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1001723 · Cited by 86
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
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
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
