title: Immune tolerance. Group 3 innate lymphoid cells mediate intestinal selection of commensal bacteria-specific CD4⁺ T cells.
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.
authors.affiliation: 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.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Hepworth
authors.affiliation: 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.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Fung
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Masur
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Judith R
authors.initials: JR
authors.lastname: Kelsen
authors.affiliation: Medical Research Council, Centre for Immune Regulation, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Fiona M
authors.initials: FM
authors.lastname: McConnell
authors.affiliation: Department of Pathology and Immunology, University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Juan
authors.initials: J
authors.lastname: Dubrot
authors.affiliation: Medical Research Council, Centre for Immune Regulation, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: David R
authors.initials: DR
authors.lastname: Withers
authors.affiliation: Department of Pathology and Immunology, University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Hugues
authors.affiliation: Center for Immunology, Department of Laboratory Medicine and Pathology, University of Minnesota, MN, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Farrar
authors.affiliation: Department of Pathology and Immunology, University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Walter
authors.initials: W
authors.lastname: Reith
authors.affiliation: Institut Pasteur, Microenvironment and Immunity Unit, Paris, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Eberl
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Baldassano
authors.affiliation: Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Philadelphia Veterans Affairs Medical Center, Philadelphia, PA, USA.
authors.forename: Terri M
authors.initials: TM
authors.lastname: Laufer
authors.affiliation: Departments of Medicine and Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Charles O
authors.initials: CO
authors.lastname: Elson
authors.affiliation: 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.
authors.forename: Gregory F
authors.initials: GF
authors.lastname: Sonnenberg
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D015551:Autoimmunity; D001419:Bacteria / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003106:Colon / Q000382:microbiology*; D005260:Female; D005408:Flagellin / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000382:microbiology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013559:Symbiosis; D013950:Thymus Gland / Q000276:immunology
chemical_list: C502160:CBir1 flagellin; D000949:Histocompatibility Antigens Class II; D005408:Flagellin