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

Hyun Ju Lee, Jung Hwa Ko, Hyun Jeong Jeong, Ah Young Ko, Mee Kum Kim, Won Ryang Wee, Sun Ok Yoon, Joo Youn Oh

Research output: Contribution to journalArticle

30 Scopus citations

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 IIlo Ly6G-Ly6ChiCD11b+ cells in draining lymph nodes by MSCs. These Ly6ChiCD11b+ cells suppressed CD4+ cell proliferation and Th1/TH17 differentiation and induced CD4+ cell apoptosis. Adoptive transfer of Ly6ChiCD11b+ cells ameliorated EAU, whereas depletion of Ly6ChiCD11b+ 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 IIloLy6G-Ly6ChiCD11b+ 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.

Original languageEnglish
Pages (from-to)3634-3645
Number of pages12
JournalJournal of Immunology
Volume194
Issue number8
DOIs
StatePublished - 15 Apr 2015

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