Format

Send to

Choose Destination
Science. 2015 May 29;348(6238):1031-5. doi: 10.1126/science.aaa4812. Epub 2015 Apr 23.

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

Author information

1
Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Gastroenterology Division, and Department of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, New York, NY, USA.
2
Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Gastroenterology Division, and Department of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, New York, NY, USA. Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
3
Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
4
Medical Research Council, Centre for Immune Regulation, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
5
Department of Pathology and Immunology, University of Geneva Medical School, Geneva, Switzerland.
6
Center for Immunology, Department of Laboratory Medicine and Pathology, University of Minnesota, MN, USA.
7
Institut Pasteur, Microenvironment and Immunity Unit, Paris, France.
8
Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Philadelphia Veterans Affairs Medical Center, Philadelphia, PA, USA.
9
Departments of Medicine and Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA.
10
Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Gastroenterology Division, and Department of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, New York, NY, USA. gfsonnenberg@med.cornell.edu.

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.

PMID:
25908663
PMCID:
PMC4449822
DOI:
10.1126/science.aaa4812
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center