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Science DOI:10.1126/science.aaa9420

MUCOSAL IMMUNOLOGY. Individual intestinal symbionts induce a distinct population of RORγ⁺ regulatory T cells.

Publication TypeJournal Article
Year of Publication2015
AuthorsSefik, E, Geva-Zatorsky, N, Oh, S, Konnikova, L, Zemmour, D, McGuire, AManson, Burzyn, D, Ortiz-Lopez, A, Lobera, M, Yang, J, Ghosh, S, Earl, A, Snapper, SB, Jupp, R, Kasper, D, Mathis, D, Benoist, C
Date Published2015 Aug 28
KeywordsAnimals, Bacteria, Bacteroidetes, Colitis, Ulcerative, Colon, Forkhead Transcription Factors, Homeostasis, Humans, Immunity, Mucosal, Intestinal Mucosa, Mice, Inbred C57BL, Microbiota, Nuclear Receptor Subfamily 1, Group F, Member 3, Symbiosis, T-Lymphocyte Subsets, T-Lymphocytes, Regulatory, Th17 Cells, Transcription, Genetic, Transcriptome

T regulatory cells that express the transcription factor Foxp3 (Foxp3(+) T(regs)) promote tissue homeostasis in several settings. We now report that symbiotic members of the human gut microbiota induce a distinct T(reg) population in the mouse colon, which constrains immuno-inflammatory responses. This induction—which we find to map to a broad, but specific, array of individual bacterial species—requires the transcription factor Rorγ, paradoxically, in that Rorγ is thought to antagonize FoxP3 and to promote T helper 17 (T(H)17) cell differentiation. Rorγ's transcriptional footprint differs in colonic T(regs) and T(H)17 cells and controls important effector molecules. Rorγ, and the T(regs) that express it, contribute substantially to regulating colonic T(H)1/T(H)17 inflammation. Thus, the marked context-specificity of Rorγ results in very different outcomes even in closely related cell types.


Alternate JournalScience
PubMed ID26272906
PubMed Central IDPMC4700932
Grant ListR01 AI110630 / AI / NIAID NIH HHS / United States
R56 AI110630 / AI / NIAID NIH HHS / United States
R01-AI51530 / AI / NIAID NIH HHS / United States
R37 AI051530 / AI / NIAID NIH HHS / United States
K01 DK102771 / DK / NIDDK NIH HHS / United States
P30 DK034854 / DK / NIDDK NIH HHS / United States
R01 AI051530 / AI / NIAID NIH HHS / United States
R56-AI110630 / AI / NIAID NIH HHS / United States