间充质干细胞（MSC）治疗临床免疫性疾病的统计结果显示：MSC的体内免疫调节效果并不理想。二级淋巴器官结构相似，由T、B、抗原呈递细胞等组成，是体内细胞和体液免疫反应启动的场所。申请人已发表工作首次证明：CCR7+MSC具有二级淋巴器官靶向迁移的特性，可在T细胞免疫的起始阶段发挥近距离高效调节。系统性红斑狼疮（SLE）是典型的B细胞活化为主的体液免疫性疾病，B细胞首先亦是在二级淋巴器官中通过T细胞依赖途径活化的。因此，我们设想：MSC输注后的靶向性二级淋巴器官迁移是提高MSC治疗SLE更为有效的途径。本课题拟进一步考察CCR7+MSC对B细胞的影响；利用体内示踪、外源细胞定量技术考察输注后的CCR7+MSC在SLE小鼠二级淋巴器官中与T、B细胞的时空动态分布规律；并进一步探索CCR7+MSC体内对B细胞体液免疫调节的关键途径及生物学机制。本研究有望为提高MSC治疗SLE效果提供新思路。

Unfortunately, though lots of evidence show that mesenchymal stem cells (MSC) have potent immunoregulatory capacity in vitro, most of clinical trials of MSCs in immune disease have only met safety endpoints, efficacy has not been demonstrated. The sites of organized lymphoid cell accumulation are termed primary and secondary lymphoid organs (SLOs). SLOs, including spleen (SP), lymphoid nodes (LN), mesenteric lymphoid nodes (MLN), Peyer’s Patches (PP), and so forth, are similarly organized with T cells, B cells, antigen presenting cells, stromal cells as well as a vascular supply. Therefore, SLOs are the niches to generate immune responses or tolerance. The reported work of applicant showed that the infused MSCs/CCR7 tartly migrate to SLOs, relocate in proximity with T lymphocytes, therefore, potently inhibited their proliferation, activation, and cytotoxicity. The infusion of MSCs/CCR7 potently prolonged the survival of GvHD mouse model than normal MSCs. Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that is known to be associated with polyclonal B-cell hyper-reactivity. B cells are initially activated by T helper cells in SLOs. Therefore, we hypothesis that it is a novel strategy to lead MSCs targeted migrate to SLOs after infusion. This project will further investigate the effect of CCR7+MSC on the B cells, the relationship of CCR7+MSC distribution pattern with T and B cells in SLOs after infusion. The detailed immunoregulatory mechanism of CCR7+MSC on B cells will also be investigated. The result of his study would provide a new method to treat SLE patient clinically.