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


ABSTRACT: 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)1?, IL6, tumour necrosis factor alpha (TNF-?), 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.

SUBMITTER: Zhang F 

PROVIDER: S-EPMC7214166 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Mesenchymal stem cells alleviate rat diabetic nephropathy by suppressing CD103<sup>+</sup> DCs-mediated CD8<sup>+</sup> T cell responses.

Zhang Fuping F   Wang Chengshi C   Wen Xin X   Chen Yang Y   Mao Ruiwen R   Cui Danli D   Li Lan L   Liu Jingping J   Chen Younan Y   Cheng Jingqiu J   Lu Yanrong Y  

Journal of cellular and molecular medicine 20200413 10


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<sup>+</sup> 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<sup>+</sup> DCs and the potential mechanisms underlying MSCs-mediated protective effects i  ...[more]

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