title: Segmented filamentous bacteria antigens presented by intestinal dendritic cells drive mucosal Th17 cell differentiation.
abstract: How commensal microbiota contributes to immune cell homeostasis at barrier surfaces is poorly understood. Lamina propria (LP) T helper 17 (Th17) cells participate in mucosal protection and are induced by commensal segmented filamentous bacteria (SFB). Here we show that MHCII-dependent antigen presentation of SFB antigens by intestinal dendritic cells (DCs) is crucial for Th17 cell induction. Expression of MHCII on CD11c(+) cells was necessary and sufficient for SFB-induced Th17 cell differentiation. Most SFB-induced Th17 cells recognized SFB in an MHCII-dependent manner. SFB primed and induced Th17 cells locally in the LP and Th17 cell induction occurred normally in mice lacking secondary lymphoid organs. The importance of other innate cells was unveiled by the finding that MHCII deficiency in group 3 innate lymphoid cells (ILCs) resulted in an increase in SFB-independent Th17 cell differentiation. Our results outline the complex role of DCs and ILCs in the regulation of intestinal Th17 cell homeostasis.
authors.affiliation: Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Goto
authors.affiliation: Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Casandra
authors.initials: C
authors.lastname: Panea
authors.affiliation: Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Gaku
authors.initials: G
authors.lastname: Nakato
authors.affiliation: Center for Biotechnology and Genomic Medicine, Georgia Regents University, Augusta, GA 30912, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Cebula
authors.affiliation: Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Lee
authors.affiliation: Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Marta Galan
authors.initials: MG
authors.lastname: Diez
authors.affiliation: Department of Medicine, Perelman School of Medicine, University of Pennsylvania and Philadelphia Veterans Affairs Medical Center, Philadelphia, PA 19104, USA.
authors.forename: Terri M
authors.initials: TM
authors.lastname: Laufer
authors.affiliation: Center for Biotechnology and Genomic Medicine, Georgia Regents University, Augusta, GA 30912, USA.
authors.forename: Leszek
authors.initials: L
authors.lastname: Ignatowicz
authors.affiliation: Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA. Electronic address: ii2137@columbia.edu.
authors.forename: Ivaylo I
authors.initials: II
authors.lastname: Ivanov
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D003013:Clostridium / Q000276:immunology*; D003015:Clostridium Infections / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism*; D007422:Intestines / Q000276:immunology* / Q000382:microbiology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D064307:Microbiota / Q000276:immunology; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D000949:Histocompatibility Antigens Class II; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3