A latest study led by Zhejiang University School of Medicine immunologists and published October 10, 2016 in Nature Communication , demonstrate that extracellular vesicles (EVs) with immunosuppressive activity mediated by TGF-β1 are produced by intestinal epithelial cells (IECs) under physiological conditions.

How the intestinal tract develops a tolerance to foreign antigens is still largely unknown. Here associated professor Cai’s group report that extracellular vesicles (EVs) with immunosuppressive activity mediated by TGF-β1 are produced by intestinal epithelial cells (IECs) under physiological conditions.  Transfer of these EVs into dextran sulfate sodium salt-induced inflammatory bowel disease (IBD) mice 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 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, their study indicates that EVs from IECs participate in maintaining intestinal tract immune balance. Increase of EV production by IECs or activation of ERK signaling in IECs may represent a promising treatment strategy of diseases caused by disruption of intestinal immunohomeostasis.

Ph.D. students Lingling Jiang, Yingying Shen and Danfeng Guo share the co-first authorship, and the whole study is led by associate professor Zhijian Cai and Prof. Jianli wang from the institute of Immunology at Zhejiang University School of Medicine. This work is supported by the National Natural Science Foundation of China.