Mesenchymal stem/stromal cells protect against autoimmunity via CCL2-dependent recruitment of myeloid-derived suppressor cells

The Journal of Immunology : Official Journal of the American Association of Immunologists
Hyun Ju LeeJoo Youn Oh

Abstract

Exogenously administered mesenchymal stem/stromal cells (MSCs) suppress autoimmunity despite transient engraftment. However, the mechanism is unclear. In this study, we report a novel mechanism by which MSCs modulate the immune system by recruiting myeloid-derived suppressor cells in a mouse model of experimental autoimmune uveitis (EAU). Intravenous infusion of MSCs blocked EAU development and reduced Th1 and Th17 responses. Time course analysis revealed an increase of MHC class II(lo)Ly6G(-)Ly6C(hi)CD11b(+) cells in draining lymph nodes by MSCs. These Ly6C(hi)CD11b(+) cells suppressed CD4(+) cell proliferation and Th1/Th17 differentiation and induced CD4(+) cell apoptosis. Adoptive transfer of Ly6C(hi)CD11b(+) cells ameliorated EAU, whereas depletion of Ly6C(hi)CD11b(+) cells abrogated the effects of MSCs. 1.8% of MSCs were present in draining lymph nodes 1 d after infusion, and MSCs with CCL2 knockdown did not increase MHC class II(lo)Ly6G(-)Ly6C(hi)CD11b(+) cells and failed to attenuate EAU. Therefore, our findings demonstrate that MSCs suppress autoimmunity by recruiting myeloid-derived suppressor cells into sites of inflammation in a CCL2-dependent manner.

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Citations

Dec 25, 2015·Proceedings of the National Academy of Sciences of the United States of America·Jung Hwa KoJoo Youn Oh
Jul 19, 2018·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Hyun Ju LeeJoo Youn Oh
Nov 29, 2017·Stem Cells International·Cosette M Rivera-CruzMarxa L Figueiredo
Dec 20, 2018·Frontiers in Immunology·Min LiShengjun Wang
Sep 19, 2020·International Journal of Molecular Sciences·Santiago RouraFrancesc E Borràs
Jan 10, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hyun Jeong JeongJoo Youn Oh
Jan 22, 2021·Cellular & Molecular Biology Letters·Wenqing LiangXuerong Chen
Mar 30, 2021·Progress in Retinal and Eye Research·Joo Youn Oh, Ryang Hwa Lee
Nov 6, 2021·Cancer Cell International·Xiuyun XuanChangzheng Huang

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