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 Armendariz, Juan; Withers, David R; Hugues, Stéphanie; Farrar, Michael A; Reith, Walter; Eberl, Gérard; Baldassano, Robert N; Laufer, Terri M; Elson, Charles O; Sonnenberg, Gregory F

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Title		Immune tolerance. Group 3 innate lymphoid cells mediate intestinal selection of commensal bacteria-specific CD4⁺ T cells
Authors		Hepworth, Matthew R Fung, Thomas C Masur, Samuel H Kelsen, Judith R McConnell, Fiona M Dubrot Armendariz, Juan Withers, David R Hugues, Stéphanie Farrar, Michael A Reith, Walter Eberl, Gérard Baldassano, Robert N Laufer, Terri M Elson, Charles O Sonnenberg, Gregory F show all authors [1 - 15]
Published in		Science. 2015, vol. 348, no. 6238, p. 1031-1035
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.
Keywords		Animals — Apoptosis/immunology — Autoimmunity — Bacteria/immunology — CD4-Positive T-Lymphocytes/immunology — Colon/microbiology — Female — Flagellin/genetics/immunology — Histocompatibility Antigens Class II/immunology — Humans — Immunity, Innate — Inflammatory Bowel Diseases/immunology/microbiology — Lymphocyte Activation — Male — Mice — Mice, Inbred C57BL — Symbiosis — Thymus Gland/immunology
Identifiers		DOI: 10.1126/science.aaa4812 PMID: 25908663
Full text		Article (Published version) (2.3 MB) - Limited access to UNIGE
Structures		Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie
Research group		Pathologie et immunologie (906)
Citation (ISO format)		HEPWORTH, Matthew R et al. Immune tolerance. Group 3 innate lymphoid cells mediate intestinal selection of commensal bacteria-specific CD4⁺ T cells. In: Science, 2015, vol. 348, n° 6238, p. 1031-1035. https://archive-ouverte.unige.ch/unige:77873