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Background  Mesenchymal stem cells (MSCs) have been recognized as a promising tool for the treatment of various inflammatory disorders and autoimmune diseases. Stress conditions affect immune-mediated treatment and activate autophagy in MSCs. However, whether autophagy affects the MSC-mediated recruitment and differentiation of CD4 +  T cells remains elusive.    Methods  MSCs were pretreated with 3-methyladenine (3-MA) and rapamycin to regulate autophagy, and then co-cultured with CD4 +  T cells. CD4 +  T cell migration and differentiation were detected by flow cytometry. Further, gene expression levels of well-known chemokines were analyzed by quantitative real-time PCR. Enzyme-linked immunosorbent assays and western blot analysis were performed to detect C-X-C motif chemokine ligand 8 (CXCL8) and transforming growth factor (TGF)-β1 protein levels. An exogenous antibody and short hairpin RNA were used to regulate CXCL8 and TGF-β1 levels, which enabled us to evaluate how autophagy affected MSC-mediated CD4 +  T cell migration and differentiation.    Results  3-MA inhibited autophagy in MSCs, which was activated by rapamycin. Rapamycin increased the migration of CD4 +  T cells, whereas 3-MA decreased their migration. Mechanistically, we found that autophagy strengthened CXCL8 secretion, and the addition of exogenous CXCL8 and an anti-CXCL8 antibody eliminated the difference of CD4 +  T cell migration among groups. Further, the ratio of regulatory T (Treg) cells was increased in rapamycin-pretreated MSCs, but the ratio of T helper 1 (Th1) cells was decreased, while pretreatment of MSCs with 3-MA induced the opposite effect compared with the control group. TGF-β1 overexpression and knockdown using lentiviruses rectified the differences in the ratios of Treg and Th1 cells among the groups.    Conclusion  This study demonstrates that autophagy of mesenchymal stem cells mediates CD4 +  T cell migration and differentiation through CXCL8 and TGF-β1, respectively. These results provide a potential new strategy for improving MSC-mediated therapy.    Electronic supplementary material  The online version of this article (10.1186/s13287-019-1380-0) contains supplementary material, which is available to authorized users.

Autophagy enhances mesenchymal stem cell-mediated CD4+ T cell migration and differentiation through CXCL8 and TGF-β1