Mesenchymal stem cells promote CD206 expression and phagocytic activity of macrophages through IL-6 in systemic lupus erythematosus

•SLE macrophages are deficient in M2 polarization and phagocytic activity.•UCMSCs promote the level of CD206 and phagocytic activity of SLE macrophages.•IL-6 is required for UCMSC mediated SLE macrophage restoration.

Human umbilical cord-derived mesenchymal stem cells (UCMSCs) show therapeutic effects on systemic lupus erythematosus (SLE). Deficiency in functional polarization and phagocytosis in macrophages has been suggested in the pathogenesis of SLE. We found that macrophages from B6.MRL-Faslpr mice exhibited lower level of CD206, the marker for alternatively activated macrophage (AAM, also called M2). In addition, the phagocytic activity of B6.MRL-Faslpr macrophages was also decreased. UCMSC transplantation improved the proportion of CD206+ macrophages and their phagocytic activity in B6.MRL-Faslpr mice. Importantly, macrophages from SLE patients also showed lower expression of CD206 and reduced phagocytic activity, which were corrected by being co-cultured with UCMSCs in vitro and in SLE patients receiving UCMSC transplantation. Mechanistically, we demonstrated that IL-6 was required for the up-regulation of CD206 expression and phagocytic activity of UCMSC-treated SLE macrophages. Our results indicate that UCMSCs alleviate SLE through promoting CD206 expression and phagocytic activity of macrophages in an IL-6 dependent manner.