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

Matthew R. Hepworth, Thomas C. Fung, Samuel H. Masur, Judith R. Kelsen, Fiona M. McConnell, Juan Dubrot, David R. Withers, Stephanie Hugues, Michael A. Farrar, Walter Reith, Gérard Eberl, Robert N. Baldassano, Terri M. Laufer, Charles O. Elson, Gregory F. Sonnenberg

Research output: Contribution to journalArticle

202 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1031-1035
Number of pages5
JournalScience
Volume348
Issue number6238
DOIs
StatePublished - May 29 2015

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    Hepworth, M. R., Fung, T. C., Masur, S. H., Kelsen, J. R., McConnell, F. M., Dubrot, J., Withers, D. R., Hugues, S., Farrar, M. A., Reith, W., Eberl, G., Baldassano, R. N., Laufer, T. M., Elson, C. O., & Sonnenberg, G. F. (2015). Group 3 innate lymphoid cells mediate intestinal selection of commensal bacteria-specific CD4+ T cells. Science, 348(6238), 1031-1035. https://doi.org/10.1126/science.aaa4812