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

• DOI: 10.18632/oncotarget.7324
• Publication Date: 2016-02-11T17:30:33Z
• Authors: Yungang Wang; Jie Tian; Xinyi Tang; Ke Rui; Xinyu Tian; Jie Ma; Bin Ma; Huaxi Xu; Liwei Lu; Shengjun Wang
• Keywords: 0301 basic medicine; Myeloid-Derived Suppressor Cells; Dextran Sulfate; Research Paper: Immunology; Th1 Cells; Colitis; Exosomes; T-Lymphocytes, Regulatory; 3. Good health; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Animals; Granulocytes

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.