G-MDSC-derived exosomes attenuate collagen-induced arthritis by impairing Th1 and Th17 cell responses

Biochim Biophys Acta Mol Basis Dis. 2019 Dec 1;1865(12):165540. doi: 10.1016/j.bbadis.2019.165540. Epub 2019 Aug 27.

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.

Keywords: Collagen-induced arthritis; Exosomes; MicroRNA; Myeloid-derived suppressor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental / chemically induced
  • Arthritis, Experimental / immunology
  • Arthritis, Experimental / therapy*
  • Cattle
  • Cells, Cultured
  • Collagen
  • Exosomes / immunology
  • Exosomes / transplantation*
  • Humans
  • Immunity, Cellular
  • Male
  • Myeloid-Derived Suppressor Cells / immunology*
  • Th1 Cells / immunology*
  • Th17 Cells / immunology*

Substances

  • Collagen