间充质干细胞免疫调节的可塑性

Plasticity of mesenchymal stem cells in immunomodulation

间充质干细胞(MSCs)因其独特的免疫调节及其他生物学特性,在组织损伤,免疫调控和再生医学领域受到了广泛的研究,并在临床试验中用于治疗一系列免疫相关的疾病.然而,临床试验结果表明,MSCs并不总是产生免疫抑制作用,有时会得到自相矛盾的结果.最近的研究发现,MSCs既可以抑制免疫应答,也可以促进免疫应答,不同的炎症介质会诱导MSCs极化分型并表现出截然相反的免疫调节作用,这一特性称为MSCs免疫调节的可塑性.本文将重点阐述炎症微环境下不同促炎因子的浓度以及自身TLR3和TLR4激活后对MSCs免疫调节可塑性所起的主导作用,特别是NO/IDO可能在MSCs从免疫抑制向免疫促进转变的过程中起到分子开关的作用.深入了解MSCs免疫调节的可塑性和极化分型的概念,可以更好地指导MSCs在临床上的应用.

Because of their unique immune regulatory effects and other biological properties, mesenchymal stem cells （MSCs） have been extensively investigated in the fields of tissue repair, immunotherapy, and regenerative medicine and have been applied in the clinical studies to treat a wide variety of immune-mediated disorders. However, the immunosuppressive function of MSCs is not always observed and MSC therapies show conflicting clinical outcomes. Recent studies have found that MSCs can either suppress or promote the immune response. Stimulation by different inflammatory mediators can induce remarkably different responses and polarization of MSCs, suggesting the immunomodulatary plasticity of MSCs. In this review, we focus on the effect of different concentrations of pro-inflammatory cytokines and the ligation of TLR3 or TLR4, which play dominate roles in orchestrating the plasticity of MSCs in immunomodulation. Particularly, we highlight the central role that NO/IDO may serve as a molecular switch between the immune-suppressive to immune-enhancing effects of MSCs. A better understanding of plasticity in immune modulation and polarization of MSCs will provide fundamental information for guiding the appropriate clinical application of MSCs.