PMID- 32283569 OWN - NLM STAT- MEDLINE DCOM- 20210430 LR - 20210430 IS - 1582-4934 (Electronic) IS - 1582-1838 (Print) IS - 1582-1838 (Linking) VI - 24 IP - 10 DP - 2020 May TI - Mesenchymal stem cells alleviate rat diabetic nephropathy by suppressing CD103(+) DCs-mediated CD8(+) T cell responses. PG - 5817-5831 LID - 10.1111/jcmm.15250 [doi] AB - 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. CI - (c) 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. FAU - Zhang, Fuping AU - Zhang F AUID- ORCID: 0000-0003-2199-4609 AD - Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China. FAU - Wang, Chengshi AU - Wang C AUID- ORCID: 0000-0002-0650-4109 AD - Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China. FAU - Wen, Xin AU - Wen X AD - Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China. FAU - Chen, Yang AU - Chen Y AD - Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China. FAU - Mao, Ruiwen AU - Mao R AD - Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China. FAU - Cui, Danli AU - Cui D AD - Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China. FAU - Li, Lan AU - Li L AD - Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China. FAU - Liu, Jingping AU - Liu J AUID- ORCID: 0000-0001-8364-639X AD - Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China. FAU - Chen, Younan AU - Chen Y AD - Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China. FAU - Cheng, Jingqiu AU - Cheng J AD - Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China. FAU - Lu, Yanrong AU - Lu Y AUID- ORCID: 0000-0002-3728-222X AD - Key Laboratory of Transplant Engineering and Immunology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200413 PL - England TA - J Cell Mol Med JT - Journal of cellular and molecular medicine JID - 101083777 RN - 0 (Antigens, CD) RN - 0 (Antigens, Differentiation, Myelomonocytic) RN - 0 (CD68 antigen, human) RN - 0 (Integrin alpha Chains) RN - 0 (alpha E integrins) SB - IM MH - Animals MH - Antigens, CD/*metabolism MH - Antigens, Differentiation, Myelomonocytic/metabolism MH - CD8-Positive T-Lymphocytes/*immunology MH - Cell Proliferation MH - Cytotoxicity, Immunologic MH - Dendritic Cells/*metabolism MH - Diabetic Nephropathies/*immunology/pathology/*therapy MH - Inflammation/pathology MH - Integrin alpha Chains/*metabolism MH - Kidney/injuries/pathology MH - Lymphocyte Activation/immunology MH - Macrophages/metabolism/pathology MH - Male MH - *Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/*metabolism MH - Models, Biological MH - Rats, Sprague-Dawley PMC - PMC7214166 OTO - NOTNLM OT - CD103+ dendritic cells OT - diabetic nephropathy OT - immunosuppression OT - kidney injury OT - mesenchymal stem cells COIS- The authors declared that there are no conflicts of interest. EDAT- 2020/04/14 06:00 MHDA- 2021/05/01 06:00 PMCR- 2020/05/01 CRDT- 2020/04/14 06:00 PHST- 2019/12/23 00:00 [received] PHST- 2020/02/27 00:00 [revised] PHST- 2020/03/15 00:00 [accepted] PHST- 2020/04/14 06:00 [pubmed] PHST- 2021/05/01 06:00 [medline] PHST- 2020/04/14 06:00 [entrez] PHST- 2020/05/01 00:00 [pmc-release] AID - JCMM15250 [pii] AID - 10.1111/jcmm.15250 [doi] PST - ppublish SO - J Cell Mol Med. 2020 May;24(10):5817-5831. doi: 10.1111/jcmm.15250. Epub 2020 Apr 13.