Title | Immune tolerance. Group 3 innate lymphoid cells mediate intestinal selection of commensal bacteria-specific CD4⁺ T cells. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Hepworth, MR, Fung, TC, Masur, SH, Kelsen, JR, McConnell, FM, Dubrot, J, Withers, DR, Hugues, S, Farrar, MA, Reith, W, Eberl, G, Baldassano, RN, Laufer, TM, Elson, CO, Sonnenberg, GF |
Journal | Science |
Volume | 348 |
Issue | 6238 |
Pagination | 1031-5 |
Date Published | 2015 May 29 |
ISSN | 1095-9203 |
Keywords | Animals, Apoptosis, Autoimmunity, Bacteria, CD4-Positive T-Lymphocytes, Colon, Female, Flagellin, Histocompatibility Antigens Class II, Humans, Immunity, Innate, Inflammatory Bowel Diseases, Lymphocyte Activation, Male, Mice, Mice, Inbred C57BL, Symbiosis, Thymus Gland |
Abstract | <p>Inflammatory CD4(+) T cell responses to self or commensal bacteria underlie the pathogenesis of autoimmunity and inflammatory bowel disease (IBD), respectively. Although selection of self-specific T cells in the thymus limits responses to mammalian tissue antigens, the mechanisms that control selection of commensal bacteria-specific T cells remain poorly understood. Here, we demonstrate that group 3 innate lymphoid cell (ILC3)-intrinsic expression of major histocompatibility complex class II (MHCII) is regulated similarly to thymic epithelial cells and that MHCII(+) ILC3s directly induce cell death of activated commensal bacteria-specific T cells. Further, MHCII on colonic ILC3s was reduced in pediatric IBD patients. Collectively, these results define a selection pathway for commensal bacteria-specific CD4(+) T cells in the intestine and suggest that this process is dysregulated in human IBD.</p> |
DOI | 10.1126/science.aaa4812 |
Alternate Journal | Science |
PubMed ID | 25908663 |
PubMed Central ID | PMC4449822 |
Grant List | DK071176 / DK / NIDDK NIH HHS / United States DP5 OD012116 / OD / NIH HHS / United States DP5OD012116 / OD / NIH HHS / United States UL1-RR024134 / RR / NCRR NIH HHS / United States / / Wellcome Trust / United Kingdom |