title: Specific microbiota-induced intestinal Th17 differentiation requires MHC class II but not GALT and mesenteric lymph nodes.
abstract: IL-17-expressing CD4+ T lymphocytes (Th17 cells) naturally reside in the intestine where specific cytokines and microbiota, such as segmented filamentous bacteria (SFB), promote their differentiation. Intestinal Th17 cells are thought to initially differentiate in the GALT and/or mesenteric lymph nodes upon Ag encounter and subsequently home to the lamina propria (LP) where they mediate effector functions. However, whether GALT and/or mesenteric lymph nodes are required for intestinal Th17 differentiation as well as how microbiota containing SFB regulate Ag-specific intestinal Th17 cells remain poorly defined. In this study, we observed that naive CD4+ T cells were abundant in the intestinal LP prior to weaning and that the accumulation of Th17 cells in response to microbiota containing SFB occurred in the absence of lymphotoxin-dependent lymphoid structures and the spleen. Furthermore, the differentiation of intestinal Th17 cells in the presence of microbiota containing SFB was dependent on MHC class II expression by CD11c+ cells. Lastly, the differentiation of Ag-specific Th17 cells required both the presence of cognate Ag and microbiota containing SFB. These findings suggest that microbiota containing SFB create an intestinal milieu that may induce Ag-specific Th17 differentiation against food and/or bacterial Ags directly in the intestinal LP.
authors.affiliation: Center for Inflammation, Immunity, and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303; Department of Pediatrics, Emory University, Atlanta, GA 30322; Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322;
authors.forename: Duke
authors.initials: D
authors.lastname: Geem
authors.affiliation: Center for Inflammation, Immunity, and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303; Department of Pediatrics, Emory University, Atlanta, GA 30322; Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322;
authors.forename: Oscar
authors.initials: O
authors.lastname: Medina-Contreras
authors.affiliation: Center for Inflammation, Immunity, and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303;
authors.forename: Michelle
authors.initials: M
authors.lastname: McBride
authors.affiliation: Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110; and.
authors.forename: Rodney D
authors.initials: RD
authors.lastname: Newberry
authors.affiliation: Cancer Immunology, Inflammation, and Tolerance Program, Georgia Regents University, Augusta, GA 30912.
authors.forename: Pandelakis A
authors.initials: PA
authors.lastname: Koni
authors.affiliation: Center for Inflammation, Immunity, and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303; Department of Pediatrics, Emory University, Atlanta, GA 30322; Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322; tdenning@gsu.edu.
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Denning
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001419:Bacteria / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D007422:Intestines / Q000276:immunology / Q000382:microbiology; D008198:Lymph Nodes / Q000276:immunology*; D008643:Mesentery / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D000949:Histocompatibility Antigens Class II