sHLA-G调控MSCs治疗SLE的疗效及其机制研究

项目名称： sHLA-G调控MSCs治疗SLE的疗效及其机制研究

项目编号： No.81202333

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学免疫学、法医学

项目作者： 梁军

作者单位： 南京大学

项目金额： 23万元

中文摘要： 近年来国内外的研究表明可溶性主要组织相容性人类白细胞抗原G（soluble HLA-G, sHLA-G）是一个较强的免疫抑制分子，它可抑制T细胞的增殖，诱导T细胞凋亡并促进T细胞分化为调节性T细胞（Treg）。系统性红斑狼疮（SLE）患者的血清sHLA-G水平明显低于正常人。最近研究发现间充质干细胞（MSCs）可分泌sHLA-G。我们使用MSCs移植SLE患者，发现移植后患者血清内sHLA-G水平明显升高，并与移植疗效呈正相关，且MSCs移植后Treg数目亦明显增多，但其中的关联及机制不清楚。本研究将探讨sHLA-G分子、MSCs、Treg细胞三者的关系，进一步阐明sHLA-G在MSCs调节免疫功能中的作用机制，为临床进行MSCs移植治疗SLE提供有力的理论依据。

中文关键词： 系统性红斑狼疮；间充质干细胞；可溶性主要组织相容性人类白细胞抗原G；移植；调节性T细胞

英文摘要： Recently, some studies have shown that soluble human histocompatibility leukocyte antigen-G (soluble HLA-G), which is remarkable lower in the serum of systemic lupus erythematosus (SLE) patients compared with that in healthy controls, exhibits strong immunosuppressive properties and is able to induce the differentiation of T regulatory cells (Treg). Other studies have found that mesenchymal stem cells (MSCs) secret sHLA-G. sHLA-G is proved to be involved in MSCs-mediated immunoreguratory, although the mechanisms have remained obscure. From 2007, allogeneic MSCs transplantation has been used in the treatment in refractory and severe SLE patients in our centre. We have found that serum levels of sHLA-G increase significantly after transplantation in some tested patients, which is positively correlated to the improvement of SLEDAI scores and serological parameters. Meanwhile, we also have discovered that the numbers of Treg increase significantly in those patients after transplantation. No one knows if there are some exact links among these phenomena. We hypothesize that sHLA-G secreted by the infused MSCs regulates T cell differentiation and increases numbers, even immunosuppressive function of Treg, which utmately improves disease activity by treating ongoing autoimmunity and maintaining immune homeostasis. There

英文关键词： systemic lupus erythematosus；mesenchymal stem cell；soluble HLA-G；transplantation；Ttreg