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

被引：113

作者：

Jiang, Lingling ^{[1
]}

Shen, Yingying ^{[1
]}

Guo, Danfeng ^{[1
]}

Yang, Diya ^{[1
]}

Liu, Jiajun ^{[1
]}

Fei, Xuefeng ^{[1
]}

Yang, Yunshan ^{[2
]}

Zhang, Buyi ^{[3
]}

Lin, Zhendong ^{[4
]}

Yang, Fei ^{[5
,6
]}

Wang, Xiaojian ^{[1
]}

Wang, Keyi ^{[7
]}

Wang, Jianli ^{[1
]}

Cai, Zhijian ^{[1
]}

机构：

[1] Zhejiang Univ, Sch Med, Inst Immunol, Hangzhou 310058, Zhejiang, Peoples R China

[2] Zhejiang Canc Hosp, Dept Chemotherapy, Hangzhou 310022, Zhejiang, Peoples R China

[3] Zhejiang Univ, Sch Med, Dept Pathol, Affiliated Hosp 2, Hangzhou 310009, Zhejiang, Peoples R China

[4] Wenzhou Med Univ, Dept Gynecol & Obstet, Affiliated Hosp 2, Wenzhou 325035, Peoples R China

[5] Zhejiang Univ, Sch Publ Hlth, Dept Nutr & Food Hyg, Hangzhou 310058, Zhejiang, Peoples R China

[6] Zhejiang Univ, Sch Publ Hlth, Chron Dis Res Inst, Hangzhou 310058, Zhejiang, Peoples R China

[7] Nanjing Med Univ, Cent Lab, Affiliated Hangzhou Hosp, Hangzhou Peoples Hosp 1, Hangzhou 310006, Zhejiang, Peoples R China

来源：

NATURE COMMUNICATIONS | 2016年 / 7卷

基金：

中国国家自然科学基金;

关键词：

REGULATORY T-CELLS; INFLAMMATORY-BOWEL-DISEASE; RETRACTED ARTICLE. SEE; DENDRITIC CELLS; AUTOIMMUNE-DISEASE; EXOSOMES; TGF-BETA-1; COLITIS; GENE; MACROPHAGES;

D O I：

10.1038/ncomms13045

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

How the intestinal tract develops a tolerance to foreign antigens is still largely unknown. Here we report that extracellular vesicles (EVs) with TGF-beta 1-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-beta 1 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.

引用

页数：15

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