Immune tolerance. Group 3 innate lymphoid cells mediate intestinal selection of commensal bacteria-specific CD4⁺ T cells.

TitleImmune tolerance. Group 3 innate lymphoid cells mediate intestinal selection of commensal bacteria-specific CD4⁺ T cells.
Publication TypeJournal Article
Year of Publication2015
AuthorsHepworth, 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
JournalScience
Volume348
Issue6238
Pagination1031-5
Date Published2015 May 29
ISSN1095-9203
KeywordsAnimals, 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>

DOI10.1126/science.aaa4812
Alternate JournalScience
PubMed ID25908663
PubMed Central IDPMC4449822
Grant ListDK071176 / 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