MSC-EVs: A Promising Modulator for Immune Response in Systemic Lupus Erythematosus

Abstract

At present, human umbilical cord mesenchymal stem cells(hUCMSCs) have been used in the clinical treatment of systemic lupus erythematosus(SLE), However, the detailed mechanism of MSCs remains unclear. In this study, we investigated whether hUCMSCs derived extracellular vesicles (hUCMSC-EVs) could regulate abnormal immune responses of T cells or B cells in SLE.We isolated splenic mononuclear cells from MRL/lpr mice , a classical animal model of SLE.PBS(Phosphate-buffered saline), 2×105 hUCMSCs, 25µg/ml hUCMSC-EVs, 50µg/ml hUCMSC-EVs were co-cultured with 2×106 activated splenic mononuclear cells for 3 days in vitro, respectively. The proportions of CD4+T cell subsets and the concentrations of cytokines were detected .Both hUCMSCs and hUCMSC-EVs inhibited CD4+T cells , increased the production of T helper(Th)17 cells , promoted the production of interleukin（IL）-17 and transforming growth factor beta 1(TGF-β1) (P＜0.05), although they had no significant effects on Th1, Th2, T follicular helper (Tfh), regulatory T (Treg )cells and IL-10 (P＞0.05);only hUCMSCs inhibited CD19+ B cells, promoted the production of interferon-gamma (IFN-γ) and IL-4 (P＜0.05).hUCMSCs exert immunoregulatory effects on SLE at least partially through hUCMSC-EVs in vitro, hUCMSC-EVs play novel and potential regulator roles in SLE.