间充质干细胞免疫抑制机制及在疾病中的应用

Mechanism of Immunosuppression and Clinical Applications of Mesenchymal Stem Cells

间充质干细胞(mesenchymal stemcells,MSCs)的分化潜能及免疫抑制能力的发现和相关研究的进展,使其有望应用于临床治疗退行性疾病和免疫失调症。MSCs发挥免疫抑制作用时,先通过免疫激活的T细胞释放IFNγ、TNFα和IL-1等细胞因子,进而刺激MSCs产生大量不同趋化因子和一氧化氮(nitricoxide,NO);趋化因子招募T细胞向MSCs聚集,MSCs生成的NO抑制T细胞增殖,产生免疫抑制效果。相关研究进展为MSCs有效应用于移植物抗宿主病(graft versus host disease,GVHD)等临床免疫性疾病治疗提供了理论指导,并展现出极大的应用前景。

The discovery of the differentiation and immunosuppression capability of mesenchymal stem cells （MSCs） makes them great candidates for treating various immune disorders such as graft versus host disease （GVHD） and autoimmune diabetes. Recent studies have shown that the immunosuppression property of MSCs is not innate, but rather induced by inflammatory cytokines （IFNγ in combination with TNFα, IL-1α, or IL-1 β） released by activated T cells. The effect of these inflammatory cytokines is exerted through the induction of MSCs to produce large amount of chemokines and nitric oxide （NO）. Chemokines drive T cell to the proximity of MSCs, whereby high concentration of NO suppresses T cell activities. These studies provide fundamental information for better clinical applications of MSCs in clinical settings.