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- PMID: 25908663
- UKPMCID: 25908663
- DOI: 10.1126/science.aaa4812
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Immune tolerance. Group 3 innate lymphoid cells mediate intestinal selection of commensal bacteria-specific CD4⁺ T cells.
Hepworth, Matthew R; Fung, Thomas C; Masur, Samuel H; Kelsen, Judith R; McConnell, Fiona M; Dubrot, Juan; Withers, David R; Hugues, Stephanie; Farrar, Michael A; Reith, Walter; Eberl, Gérard; Baldassano, Robert N; Laufer, Terri M; Elson, Charles O; Sonnenberg, Gregory F
Science (New York, N.Y.). 2015;348(6238):1031-5.
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Full-text held externally
- PMID: 25908663
- UKPMCID: 25908663
- DOI: 10.1126/science.aaa4812
Abstract
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.