Mesenchymal stem cells alleviate rat diabetic nephropathy by suppressing CD103+ DCs-mediated CD8+ T cell responses.
Fuping ZhangChengshi WangXin WenYang ChenRuiwen MaoDanli CuiLan LiJingping LiuYounan ChenJingqiu ChengYanrong LuPublished in: Journal of cellular and molecular medicine (2020)
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)1β, IL6, tumour necrosis factor alpha (TNF-α), 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.
Keyphrases
- mesenchymal stem cells
- umbilical cord
- bone marrow
- tyrosine kinase
- diabetic nephropathy
- dendritic cells
- chronic kidney disease
- transcription factor
- binding protein
- cell therapy
- cell proliferation
- epidermal growth factor receptor
- nk cells
- immune response
- gene expression
- end stage renal disease
- acute myeloid leukemia
- oxidative stress
- rheumatoid arthritis
- adipose tissue
- genome wide
- dna binding
- dna methylation
- endoplasmic reticulum stress
- metabolic syndrome
- glycemic control
- peritoneal dialysis
- cell cycle
- heat shock protein
- long non coding rna