Publication Date:
2015-08-15
Description:
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 Rorgamma, paradoxically, in that Rorgamma is thought to antagonize FoxP3 and to promote T helper 17 (T(H)17) cell differentiation. Rorgamma's transcriptional footprint differs in colonic T(regs) and T(H)17 cells and controls important effector molecules. Rorgamma, 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 Rorgamma results in very different outcomes even in closely related cell types.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4700932/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4700932/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sefik, Esen -- Geva-Zatorsky, Naama -- Oh, Sungwhan -- Konnikova, Liza -- Zemmour, David -- McGuire, Abigail Manson -- Burzyn, Dalia -- Ortiz-Lopez, Adriana -- Lobera, Mercedes -- Yang, Jianfei -- Ghosh, Shomir -- Earl, Ashlee -- Snapper, Scott B -- Jupp, Ray -- Kasper, Dennis -- Mathis, Diane -- Benoist, Christophe -- R01 AI110630/AI/NIAID NIH HHS/ -- R01-AI51530/AI/NIAID NIH HHS/ -- R37 AI051530/AI/NIAID NIH HHS/ -- R56 AI110630/AI/NIAID NIH HHS/ -- R56-AI110630/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2015 Aug 28;349(6251):993-7. doi: 10.1126/science.aaa9420. Epub 2015 Aug 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston 02115, MA, USA. ; Division of Gastroenterology and Hepatology, Brigham and Women's Hospital, Boston, MA 02115, USA, and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA. ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. ; Tempero Pharmaceuticals, a GSK Company, Cambridge, MA 02115, USA. ; UCB Pharma, Slough, Berkshire, UK. ; Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston 02115, MA, USA. Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA. cbdm@hms.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26272906" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Bacteria/immunology
;
Bacteroidetes/immunology/physiology
;
Colitis, Ulcerative/immunology
;
Colon/*immunology/microbiology
;
Forkhead Transcription Factors/analysis/metabolism
;
Homeostasis
;
Humans
;
*Immunity, Mucosal
;
Intestinal Mucosa/*immunology/microbiology
;
Mice, Inbred C57BL
;
Microbiota/*immunology/physiology
;
Nuclear Receptor Subfamily 1, Group F, Member 3/genetics/*metabolism
;
Symbiosis
;
T-Lymphocyte Subsets/immunology
;
T-Lymphocytes, Regulatory/*immunology
;
Th17 Cells/immunology
;
Transcription, Genetic
;
Transcriptome
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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