Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
Volume 1865, Issue 12, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.bbadis.2019.165540
Keywords
Myeloid-derived suppressor cells; Exosomes; MicroRNA; Collagen-induced arthritis
Funding
- National Natural Science Foundation of China [31470881, 31711530025, 81771759]
- Jiangsu Province's Key Medical Talents Program [ZDRCB2016018]
- Jiangsu Province 333 Project [BRA2017128]
- Priority Academic Program Development of Jiangsu Higher Education Institutions
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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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