title: TGF-β Signaling in Dendritic Cells Governs Colonic Homeostasis by Controlling Epithelial Differentiation and the Luminal Microbiota.
abstract: Dendritic cells (DCs) mediate host immune responses to gut microbes and play critical roles in inflammatory bowel disease. In this study, we examined the role of TGF-β signaling in DCs in colonic homeostasis. CD11c-cre Tgfbr2(fl/fl) mice developed spontaneous colitis, and CD11c-cre Tgfbr2(fl/+) mice exhibited susceptibility to dextran sulfate sodium-induced colitis. Colitis in these mice was characterized by goblet cell depletion and dysbiosis caused by Enterobacteriaceae enrichment. Wild-type mice gavaged with Enterobacteriaceae from CD11c-cre Tgfbr2(fl/fl) mice feces showed severe colitis after dextran sulfate sodium treatment, whereas those treated with Notch inhibitor exhibited attenuated colonic injury with increased goblet cell numbers, thickened mucus layer, and fewer fecal Enterobacteriaceae Wild-type mice transplanted with CD11c-cre Tgfbr2(fl/fl) bone marrow developed colitis showing increased Jagged1 and Jagged2 in DCs, increased Hes1 levels in epithelium, and goblet cell depletion. These findings suggest that TGF-β signaling in DCs regulates intestinal homeostasis by modulating epithelial cell differentiation and fecal microbiota.
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Sozaburo
authors.initials: S
authors.lastname: Ihara
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan hiratay-int@h.u-tokyo.ac.jp.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hirata
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Serizawa
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Nobumi
authors.initials: N
authors.lastname: Suzuki
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Sakitani
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Kinoshita
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Yoku
authors.initials: Y
authors.lastname: Hayakawa
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Nakagawa
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Ijichi
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Tateishi
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Koike
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000382:microbiology; D003106:Colon / Q000166:cytology* / Q000276:immunology / Q000382:microbiology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000166:cytology*; D000069196:Gastrointestinal Microbiome / Q000276:immunology; D006706:Homeostasis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000276:immunology*
chemical_list: D016212:Transforming Growth Factor beta; D016264:Dextran Sulfate