1型糖尿病CD26在骨髓MSCs抑制CD4+T/CD8+T细胞活化中的作用及机制研究

项目名称： 1型糖尿病CD26在骨髓MSCs抑制CD4+T/CD8+T细胞活化中的作用及机制研究

项目编号： No.81500638

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 李莉蓉

作者单位： 苏州卫生职业技术学院

项目金额： 18万元

中文摘要： 骨髓间充质干细胞（MSCs）移植治疗1型糖尿病（T1DM）是再生医学领域的重要分支。我们前期研究显示，骨髓MSCs治疗T1DM疗效良好但存在个体差异, 这种差异取决于MSCs对CD4+T/CD8+T细胞免疫抑制作用的差异；提高MSCs向胰岛归巢是增强MSCs免疫抑制作用的关键。研究报道CD26可降低MSCs归巢，促进CD4+T/CD8+T细胞活化。我们发现，T1DM患者或NOD小鼠（T1DM动物模型）体内CD26活性呈差异性升高，且与MSCs疗效显著负相关；CD26抑制剂可增强MSCs对CD26高活性NOD小鼠的疗效。因此推测：CD26活性差异是导致骨髓MSCs疗效差异的重要因素。本研究确立CD26与MSCs疗效相关性，观察CD26对MSCs归巢和MSCs抑制CD4+T/CD8+T细胞活化的影响，并探讨这种影响效应的分子机制。旨在寻找有效干预靶点，推动MSCs治疗T1DM的临床转化。

中文关键词： 1型糖尿病；间充质干细胞；CD26；免疫抑制

英文摘要： Mesenchymal stem cells (MSCs) transplantation for the treatment of type 1 diabetes mellitus (T1DM) is an important branch in the field of regenerative medicine. In the preliminary studies, we have confirmed the efficacy of MSCs transplantation for the treatment of T1DM, which showed obvious individual differences. The individual difference in the efficacy was attributed to the significant heterogeneity in the inhibition of CD4+T/CD8+T cells by MSCs, and the homing efficiency of bone marrow MSCs was the key factor to enhance the immunosuppressive effects of MSCs. It has been reported that CD26 activity could reduce MSCs homing, and promote CD4+T/CD8+T cells activation. We found that there was obvious heterogeneity in the CD26 activity among different T1DM patients or NOD mice, and CD26 activity was negatively related to the effects of MSCs. CD26 inhibitor enhanced the effects of MSCs in NOD mice with high CD26 activity. Therefore we speculated that the difference in CD26 activity was the key factor leading to the heterogeneity in the effects of bone marrow MSCs therapy. In view of this, our study will establish the correlation between CD26 activity and MSCs efficacy, observe the influence of CD26 activity on the homing and immunosuppressive effects of MSCs, and explore the molecular mechanisms of the influence by CD26. The aim of our study is to find the effective intervention target, which will help to promote the clinical transformation of MSCs transplantation for T1DM therapy.

英文关键词： Type 1 diabetes;Mesenchymal stem cells;CD26;Immunosuppression