title: EpCAM-dependent extracellular vesicles from intestinal epithelial cells maintain intestinal tract immune balance.
abstract: How the intestinal tract develops a tolerance to foreign antigens is still largely unknown. Here we report that extracellular vesicles (EVs) with TGF-β1-dependent immunosuppressive activity are produced by intestinal epithelial cells (IECs) under physiological conditions. Transfer of these EVs into inflammatory bowel disease (IBD) mice induced by dextran sulfate sodium salt decreases IBD severity by inducing regulatory T cells and immunosuppressive dendritic cells. In contrast, decreased endogenous EV production promotes IBD development. IECs produce EVs with increased levels of TGF-β1 upon IBD development in an ERK-dependent manner. Furthermore, these EVs tend to localize in the intestinal tract associated with epithelial cell adhesion molecule (EpCAM). Knockdown of EpCAM in vivo increases the severity of murine IBD, and the protective effect of EVs from IECs with decreased EpCAM on murine IBD is blunted. Therefore, our study indicates that EVs from IECs participate in maintaining the intestinal tract immune balance.
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Danfeng
authors.initials: D
authors.lastname: Guo
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Diya
authors.initials: D
authors.lastname: Yang
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Jiajun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Fei
authors.affiliation: Department of Chemotherapy, Zhejiang Cancer Hospital, Hangzhou 310022, China.
authors.forename: Yunshan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pathology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
authors.forename: Buyi
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Gynecology and Obstetrics, Second Affiliated Hospital, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Zhendong
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Department of Nutrition and Food Hygiene, Zhejiang University School of Public Health, Hangzhou 310058, China.|Chronic Disease Research Institute, Zhejiang University School of Public Health, Hangzhou 310058, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yang
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Xiaojian
authors.initials: X
authors.lastname: Wang
authors.affiliation: Central Laboratory, Nanjing Medical University, Affiliated Hangzhou Hospital (Hangzhou First People's Hospital), Hangzhou 310006, China.
authors.forename: Keyi
authors.initials: K
authors.lastname: Wang
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Jianli
authors.initials: J
authors.lastname: Wang
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Cai
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000378:metabolism / Q000473:pathology; D000071858:Epithelial Cell Adhesion Molecule / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism* / Q000648:ultrastructure; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D000067128:Extracellular Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D007422:Intestines / Q000276:immunology* / Q000473:pathology* / Q000648:ultrastructure; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D012720:Severity of Illness Index; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D000071858:Epithelial Cell Adhesion Molecule; D053773:Transforming Growth Factor beta1; D048049:Extracellular Signal-Regulated MAP Kinases