MSCs relieve SLE by modulation of Th17 cells through MMPs–CCL2–CCR2–IL-17 pathway

Objective:To explore the modulation of mesenchymal stem cells(MSCs)on T helper 17(Th17)cells in systemic lupus erythematosus(SLE)and underlying mechanism.Methods:The concentration of matrix metalloproteinases(MMPs),CC chemokine ligand-2(CCL2),and interleukin-17(IL-17)in the serum of SLE patients and mice were detected by enzyme-linked immunosorbent assay.The expression of CCR2 and IL-17 of T lymphocytes were determined by flow cytometry.The effects of MSCs on Th17 cells were analyzed in lupus mice and coculture system in vitro.Results:The levels of MMPs,CCL2,IL-17,CCR2,and percentages of Th17 cells were significantly increased in SLE patients.These molecules and numbers of Th17 cells were downregulated by umbilical cord-derived MSCs(UC-MSCs)which relieve SLE disease.CCL2 neutralizing antibody blocked the effects of MSCs on Th17 cells.MMPs reversed the function of CCL2.Conclusion:The beneficial effects of MSCs on SLE patients rely on secreting MMPs,which reverse the activity of CCL2 to inhibit Th17 cells,suggesting the crucial MSCs–MMP–CCL2–CCR2–Th17–IL-17 pathway in SLE.