PMID- 27183608 OWN - NLM STAT- MEDLINE DCOM- 20170928 LR - 20180121 IS - 1550-6606 (Electronic) IS - 0022-1767 (Linking) VI - 196 IP - 11 DP - 2016 Jun 1 TI - TGF-beta Signaling in Dendritic Cells Governs Colonic Homeostasis by Controlling Epithelial Differentiation and the Luminal Microbiota. PG - 4603-13 LID - 10.4049/jimmunol.1502548 [doi] AB - 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-beta 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-beta signaling in DCs regulates intestinal homeostasis by modulating epithelial cell differentiation and fecal microbiota. CI - Copyright (c) 2016 by The American Association of Immunologists, Inc. FAU - Ihara, Sozaburo AU - Ihara S AD - Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan. FAU - Hirata, Yoshihiro AU - Hirata Y AD - Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan hiratay-int@h.u-tokyo.ac.jp. FAU - Serizawa, Takako AU - Serizawa T AD - Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan. FAU - Suzuki, Nobumi AU - Suzuki N AD - Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan. FAU - Sakitani, Kosuke AU - Sakitani K AD - Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan. FAU - Kinoshita, Hiroto AU - Kinoshita H AD - Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan. FAU - Hayakawa, Yoku AU - Hayakawa Y AD - Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan. FAU - Nakagawa, Hayato AU - Nakagawa H AD - Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan. FAU - Ijichi, Hideaki AU - Ijichi H AD - Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan. FAU - Tateishi, Keisuke AU - Tateishi K AD - Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan. FAU - Koike, Kazuhiko AU - Koike K AD - Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160422 PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Transforming Growth Factor beta) RN - 9042-14-2 (Dextran Sulfate) SB - IM MH - Animals MH - Cell Differentiation MH - Colitis/chemically induced/immunology/microbiology MH - Colon/*cytology/immunology/*microbiology MH - Dendritic Cells/immunology/*metabolism MH - Dextran Sulfate MH - Disease Models, Animal MH - Epithelial Cells/*cytology MH - *Gastrointestinal Microbiome/immunology MH - *Homeostasis MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - *Signal Transduction MH - Transforming Growth Factor beta/*immunology EDAT- 2016/05/18 06:00 MHDA- 2017/09/29 06:00 CRDT- 2016/05/17 06:00 PHST- 2015/12/07 00:00 [received] PHST- 2016/03/21 00:00 [accepted] PHST- 2016/05/17 06:00 [entrez] PHST- 2016/05/18 06:00 [pubmed] PHST- 2017/09/29 06:00 [medline] AID - jimmunol.1502548 [pii] AID - 10.4049/jimmunol.1502548 [doi] PST - ppublish SO - J Immunol. 2016 Jun 1;196(11):4603-13. doi: 10.4049/jimmunol.1502548. Epub 2016 Apr 22.