G-MDSC-derived exosomes attenuate collagen-induced arthritis by impairing Th1 and Th17 cell responses.
Zhu D1, Tian J2, Wu X2, Li M2, Tang X3, Rui K4, Guo H2, Ma J2, Xu H2, Wang S5.
Author information
1Department of Laboratory Medicine, The Affiliated People’s Hospital, Jiangsu University, Zhenjiang, China; Department of Immunology, Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China.2Department of Immunology, Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China.3Department of Laboratory Medicine, The Affiliated People’s Hospital, Jiangsu University, Zhenjiang, China.4Department of Laboratory Medicine, The Affiliated Hospital of Jiangsu University, Zhenjiang, China.5Department of Laboratory Medicine, The Affiliated People’s Hospital, Jiangsu University, Zhenjiang, China; Department of Immunology, Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China. Electronic address: sjwjs@ujs.edu.cn.
Abstract
The therapeutic effect of myeloid-derived suppressor cells (MDSCs) in mice with collagen-induced arthritis (CIA) remains controversial. We analyzed the role of exosomes derived from granulocytic MDSCs (G-MDSCs) in CIA and explored the potential mechanism underlying the immunosuppressive effect. In CIA mice, G-MDSC-derived exosomes (G-exo) efficiently reduced the mean arthritis index, leukocyte infiltration and joint destruction. G-exo decreased the percentages of Th1 and Th17 cells both in vivo and in vitro. The miR-29a-3p and miR-93-5p contained in G-exo were verified to inhibit Th1 and Th17 cell differentiation by targeting T-bet and STAT3, respectively. Notably, the delivery of exogenous miR-29a-3p and miR-93-5p enhanced the ability of bone marrow-derived G-exo to attenuate arthritis progression in CIA mice. Exosomes derived from human MDSCs, which overexpressed miR-29a-3p and miR-93-5p, suppressed Th1 and Th17 cell differentiation in vitro. These data showed that G-exo alleviated CIA by suppressing Th1 and Th17 cell responses. Mechanistically, miR-29a-3p and miR-93-5p were verified to inhibit the differentiation of Th1 and Th17 cells, respectively. Our findings demonstrated the therapeutic potential of G-MDSC-derived exosomal miRNAs in autoimmune arthritis.
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KEYWORDS:
Collagen-induced arthritis; Exosomes; MicroRNA; Myeloid-derived suppressor cells