Exosomes released by granulocytic myeloid-derived suppressor cells attenuate DSS-induced colitis in mice

Abstract

// Yungang Wang 1, 2, * , Jie Tian 2, * , Xinyi Tang 1, * , Ke Rui 2 , Xinyu Tian 2 , Jie Ma 2 , Bin Ma 2 , Huaxi Xu 2 , Liwei Lu 3 , Shengjun Wang 1, 2 1 Department of Laboratory Medicine, The Affiliated People’s Hospital, Jiangsu University, Zhenjiang, China 2 Institute of Laboratory Medicine, Jiangsu Key Laboratory of Laboratory Medicine, Jiangsu University, Zhenjiang, China 3 Department of Pathology, The University of Hong Kong, Hong Kong, China * These authors contributed equally to this work Correspondence to: Shengjun Wang, e-mail: sjwjs@ujs.edu.cn Keywords: inflammatory bowel disease, exosomes, myeloid-derived suppressor cells, inflammation, Immunology and Microbiology Section, Immune response, Immunity Received: November 09, 2015      Accepted: January 29, 2016      Published: February 11, 2016 ABSTRACT Myeloid-derived suppressor cells (MDSC) have been described in inflammatory bowel disease (IBD), but their role in the disease remains controversial. We sought to define the effect of granulocytic MDSC-derived exosomes (G-MDSC exo) in dextran sulphate sodium (DSS)-induced murine colitis. G-MDSC exo-treated mice showed greater resistance to colitis, as reflected by lower disease activity index, decreased inflammatory cell infiltration damage. There was a decrease in the proportion of Th1 cells and an increase in the proportion of regulatory T cells (Tregs) in mesenteric lymph nodes (MLNs) from G-MDSC exo-treated colitis mice. Moreover, lower serum levels of interferon (IFN)-γ and tumor necrosis factor (TNF)-α were detected in G-MDSC exo-treated colitis mice. Interestingly, inhibition of arginase (Arg)-1 activity in G-MDSC exo partially abrogated the spontaneous improvement of colitis. In addition, G-MDSC exo could suppress CD4 + T cell proliferation and IFN-γ secretion in vitro and inhibit the delayed-type hypersensitivity (DTH) response, and these abilities were associated with Arg-1 activity. Moreover, G-MDSC exo promoted the expansion of Tregs in vitro . Taken together, these results suggest that G-MDSC exo attenuate DSS-induced colitis through inhibiting Th1 cells proliferation and promoting Tregs expansion.