Mesenchymal stem cells alleviate rat diabetic nephropathy by suppressing CD103(+) DCs-mediated CD8(+) T cell responses.

Diabetic nephropathy (DN) as a kind of serious microvascular complication of Diabetes Mellitus (DM) usually causes the end-stage of renal disease (ESRD). Studies have demonstrated that CD103(+) dendritic cells (DCs) exhibited a renal pathogenic effect in murine chronic kidney disease (CKD). Mesenchymal stem cells (MSCs) can alleviate DN and suppress the DCs maturation. To explore the role of CD103(+) DCs and the potential mechanisms underlying MSCs-mediated protective effects in DN, we used bone marrow MSCs (BM-MSCs) to treat DN rats. MSCs transplantation considerably recovered kidney function and diminished renal injury, fibrosis and the population of renal CD103(+) DCs in DN rat. The MSCs-treated DN rats had decreased mRNA expression levels of interleukin (IL)1beta, IL6, tumour necrosis factor alpha (TNF-alpha), monocyte chemotactic protein 1 (MCP-1) and reduced CD8 T cell infiltration in the kidney. MSCs significantly down-regulated the genes expression of transcription factors (Basic leucine zipper transcriptional factor ATF-like 3, Batf3 and DNA-binding protein inhibitor ID-2, Id2) and FMS-like tyrosine kinase-3 (Flt3) which are necessary for CD103(+) DCs development. The protective effect of MSCs may be partly related to their immunosuppression of CD8(+) T cell proliferation and activation mediated by CD103(+) DCs in the kidney of DN rats.