ArticleNature2011
Peripheral education of the immune system by colonic commensal microbiota.
Article in Nature, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 631 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
631 citing papers in PubMed, 1,027 citations in OpenAlex.
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- Intestinal T cells in aging: implications for gut barrier integrity and inflammaging.GeroScience · 2026Review
- CNS1-dependent regulatory T cells shape recovery from acute lung injury.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
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- Strain-level antigen variation facilitates immune evasion in Bacteroides thetaiotaomicron.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- The Dynamic Gut Microbiota: Monitoring Alterations During Lung Cancer Progression for Diagnosis and Precision Medicine.International journal of molecular sciences · 2026Review
- Rationally Designed Dual Kinase Inhibitors for Management of Obstructive Sleep Apnea-A Computational Study.Biomedicines · 2026Article
- Decoding Treg diversity and dysfunction to advance Treg-based therapies in autoimmune and inflammatory diseases.Frontiers in immunology · 2026Review
- Nutrition and the gut microbiome: a symbiotic dialogue influencing health and disease.Frontiers in nutrition · 2026Review
- Impact of exercise intervention on immune function during aging.Frontiers in immunology · 2026Review
- Live biotherapeuticGut microbes · 2025Article
- C10ORF99 (GPR15L) increases susceptibility to colitis and colitis-induced colorectal cancer via GPR15-independent mechanisms, while mediating GPR15-dependent T cell migration to the large intestine.Mucosal immunology · 2025Article
- Microbiota interaction with Tregs: a target for colitis.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- Salmonella-superspreader hosts require gut regulatory T cells to maintain a disease-tolerant state.The Journal of experimental medicine · 2025Article
- Beyond the tumor: the gut microbiome as a key player in immunotherapy efficacy and resistance.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Functional Specialization and Collaboration of cDC2 Subsets in CD4+ T Cell Priming and Differentiation.Immunological reviews · 2025Review
571 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The instruction of the immune system to be tolerant of self, thereby preventing autoimmunity, is facilitated by the education of T cells in a specialized organ, the thymus, in which self-reactive cells are either eliminated or differentiated into tolerogenic Foxp3(+) regulatory T (T(reg)) cells. However, it is unknown whether T cells are also educated to be tolerant of foreign antigens, such as those from commensal bacteria, to prevent immunopathology such as inflammatory bowel disease. Here we show that encounter with commensal microbiota results in the peripheral generation of T(reg) cells rather than pathogenic effectors. We observed that colonic T(reg) cells used T-cell antigen receptors (TCRs) different from those used by T(reg) cells in other locations, implying an important role for local antigens in shaping the colonic T(reg)-cell population. Many of the local antigens seemed to be derived from commensal bacteria, on the basis of the in vitro reactivity of common colon T(reg) TCRs. These TCRs did not facilitate thymic T(reg)-cell development, implying that many colonic T(reg) cells arise instead by means of antigen-driven peripheral T(reg)-cell development. Further analysis of two of these TCRs by the creation of retroviral bone marrow chimaeras and a TCR transgenic line revealed that microbiota indigenous to our mouse colony was required for the generation of colonic T(reg) cells from otherwise naive T cells. If T cells expressing these TCRs fail to undergo T(reg)-cell development and instead become effector cells, they have the potential to induce colitis, as evidenced by adoptive transfer studies. These results suggest that the efficient peripheral generation of antigen-specific populations of T(reg) cells in response to an individual's microbiota provides important post-thymic education of the immune system to foreign antigens, thereby providing tolerance to commensal microbiota.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.