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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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How gut microbiota may impact ocular surface homeostasis and related disorders
Labétoulle, M., Baudouin, C., del Castillo, J. M. B., Rolando, M., Rescigno, M., Messmer, E. S. B. M., & Aragona, P. (2024) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2024.101250 · Cited by 38
Microbiota RORgulates intestinal suppressor T cells
Hegazy, A. N., & Powrie, F. M. (2015) · Science · doi:10.1126/science.aad0865 · Cited by 36
Gut Microbiome Modulation for Preventing and Treating Pediatric Food Allergies
Costanzo, M. D., Carucci, L. R., Canani, R. B., & Biasucci, G. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21155275 · Cited by 36
“Microbiota-induced Treg cells express the nuclear hormone receptor RORγt and differentiate along a pathway that also leads to Th17 cells; in contrast, in the absence of RORγt in Treg cells there is an expansion of GATA-3-expressing Treg cells and conventional Th2 cells, and Th2-associated pathology is exacerbated [34].”
BackgroundRegulation of tissue-resident memory T cells by the Microbiota
Overacre-Delgoffe, A. E., & Hand, T. W. (2022) · Mucosal Immunology · doi:10.1038/s41385-022-00491-1 · Cited by 40
Rewiring host–microbe interactions and barrier function during gastrointestinal inflammation
Yang-Jensen, S. K., Pærregaard, S. I., Brandum, E. P., Jørgensen, A. S., Hjortø, G. M., & Jensen, B. A. H. (2022) · Gastroenterology report · doi:10.1093/gastro/goac008 · Cited by 38
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Metabolic Controls on Epigenetic Reprogramming in Regulatory T Cells
Lü, J., Liang, Y., Meng, H., Zhang, A., Zhao, J., & Zhang, C. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.728783 · Cited by 34
Gut microbiota in patients with COVID-19 and type 2 diabetes: A culture-based method
Petakh, P., Kobyliak, N. M., & Kamyshnyi, O. (2023) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2023.1142578 · Cited by 35
“RORgt+ Foxp3+ Treg cells downregulate TH1-, TH2-, and TH17 cell-type immune responses (Ohnmacht et al., 2015; Sefik et al., 2015).”
BackgroundGut microbiota-derived lipid metabolites facilitate regulatory T cell differentiation
Shiratori, H., Oguchi, H., Isobe, Y., Han, K., Sen, A., Yakebe, K., Takahashi, D., Fukushima, M., Arita, M., & Hase, K. (2023) · Scientific Reports · doi:10.1038/s41598-023-35097-5 · Cited by 35
Self-citationGut microbiota promotes immune tolerance at the maternal-fetal interface
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CD4+T Cell Fate in Glomerulonephritis: A Tale of Th1, Th17, and Novel Treg Subtypes
Krebs, C. F., & Steinmetz, O. M. (2016) · Mediators of Inflammation · doi:10.1155/2016/5393894 · Cited by 35
Microbiota and Type 2 immune responses
McCoy, K. D., Ignácio, A., & Geuking, M. B. (2018) · Current Opinion in Immunology · doi:10.1016/j.coi.2018.05.009 · Cited by 36
Sreng, N., Champion, S., Martin, J., Khelaifia, S., Christensen, J. E., Padmanabhan, R., Azalbert, V., Blasco‐Baqué, V., Loubières, P., Pechère, L., et al. (2019) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2019.108218 · Cited by 34
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Buffering Adaptive Immunity by Hydrogen Sulfide
Pozzi, G., Gobbi, G., Masselli, E., Carubbi, C., Presta, V., Ambrosini, L., Vitale, M., & Mirandola, P. (2022) · Cells · doi:10.3390/cells11030325 · Cited by 36
TREGking From Gut to Brain: The Control of Regulatory T Cells Along the Gut-Brain Axis
Choi, J., Kim, B., Akuzum, B., Chang, L., Lee, J., & Kwon, H. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.916066 · Cited by 38
“While Tregs in lymphoid organs mainly express self-antigen specific T cell receptors (TCRs), substantial number of intestinal Tregs have a set of TCRs specific for intestinal antigens which is essential to suppress immune responses against harmless dietary antigens and commensal microorganisms (26, 27).”
BackgroundGut microbiota modulate host immune cells in cancer development and growth
Erdman, S. E., & Poutahidis, T. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.11.013 · Cited by 35
Context-Dependent Regulation of Type17 Immunity by Microbiota at the Intestinal Barrier
Akuzum, B., & Lee, J. (2022) · Immune Network · doi:10.4110/in.2022.22.e46 · Cited by 36
“Numerous subsequent studies in mice (26-31) have shown that intestinal microbiota and the ability of the host to recognize and respond to its constituents are important in the generation and optimal function of local immune cells, especially Th17 cells and peripheral regulatory T cells.”
BackgroundNew insights into basophil heterogeneity
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Regulation of oral antigen delivery early in life: Implications for oral tolerance and food allergy
Yokanovich, L. T., Newberry, R. D., & Knoop, K. A. (2021) · Clinical & Experimental Allergy · doi:10.1111/cea.13823 · Cited by 37
Xenobiotic Receptor-Mediated Regulation of Intestinal Barrier Function and Innate Immunity
Ranhotra, H. S., Flannigan, K. L., Brave, M., Mukherjee, S., Lukin, D. J., Hirota, S. A., & Mani, S. (2016) · Nuclear Receptor Research · doi:10.11131/2016/101199 · Cited by 37
“Intestinal RORγt expression in Treg cells was shown to be regulated by the microbial metabolite butyrate and retinoic acid which can have important consequences in intestinal innate immunity [189, 190].”
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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