EpCAM-dependent extracellular vesicles from intestinal epithelial cells maintain intestinal tract immune balance

Lingling Jiang, Yingying Shen, Danfeng Guo, Diya Yang, Jiajun Liu, Xuefeng Fei, Yunshan Yang, Buyi Zhang, Zhendong Lin, Fei Yang, Xiaojian Wang, Keyi Wang, Jianli Wang () and Zhijian Cai ()
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Lingling Jiang: Institute of Immunology, Zhejiang University School of Medicine
Yingying Shen: Institute of Immunology, Zhejiang University School of Medicine
Danfeng Guo: Institute of Immunology, Zhejiang University School of Medicine
Diya Yang: Institute of Immunology, Zhejiang University School of Medicine
Jiajun Liu: Institute of Immunology, Zhejiang University School of Medicine
Xuefeng Fei: Institute of Immunology, Zhejiang University School of Medicine
Yunshan Yang: Zhejiang Cancer Hospital
Buyi Zhang: Second Affiliated Hospital, Zhejiang University School of Medicine
Zhendong Lin: Second Affiliated Hospital, Wenzhou Medical University
Fei Yang: Zhejiang University School of Public Health
Xiaojian Wang: Institute of Immunology, Zhejiang University School of Medicine
Keyi Wang: Central Laboratory, Nanjing Medical University, Affiliated Hangzhou Hospital (Hangzhou First People's Hospital)
Jianli Wang: Institute of Immunology, Zhejiang University School of Medicine
Zhijian Cai: Institute of Immunology, Zhejiang University School of Medicine

Nature Communications, 2016, vol. 7, issue 1, 1-16

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms13045

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