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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
Withers, David R
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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 AnimalsApoptosis/immunologyAutoimmunityBacteria/immunologyCD4-Positive T-Lymphocytes/immunologyColon/microbiologyFemaleFlagellin/genetics/immunologyHistocompatibility Antigens Class II/immunologyHumansImmunity, InnateInflammatory Bowel Diseases/immunology/microbiologyLymphocyte ActivationMaleMiceMice, Inbred C57BLSymbiosisThymus Gland/immunology
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PMID: 25908663
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Research group Pathologie et immunologie (906)
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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

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Deposited on : 2015-11-30

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