Mesenchymal stem cells (MSCs) undergo self-renewal and differentiation into multiple lineages. They exert anti-inflammatory and immunomodulatory effects via either cell-cell contact or via the production of soluble factors. Various anti-inflammatory and immunomodulatory mechanisms have been identified using experimental murine MSCs. The most representative mechanism is the induction of FOXP3+ regulatory T cells (Treg cells) via the production of transforming growth factor (TGF)-β, which has also been reported in human MSCs. Recent studies have demonstrated that insulin-like growth factor (IGF) is also involved in the induction of FOXP3+ Treg cells. We previously demonstrated that the induction of FOXP3+ Treg cells by IGF is suppressed by the expression of IGF-binding protein-4 (IGFBP-4), which is an inhibitor of IGF. Because human MSCs produce both IGFs and IGFBP4, they may be considered to maintain immunological homeostasis by positive regulation of Treg cells through the production of growth factors as well as by a negative regulatory mechanism. Although human MSCs have already been applied in regenerative therapy and autoimmune disease treatment, control of their positive and negative regulatory mechanisms is expected to lead to more efficient clinical applications.

中文翻译：

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通过人间充质干细胞释放的生长因子诱导调节性T细胞的调节机制。

间充质干细胞（MSCs）进行自我更新并分化为多个谱系。它们通过细胞间接触或通过可溶性因子的产生发挥抗炎和免疫调节作用。使用实验鼠MSC已经鉴定了多种抗炎和免疫调节机制。最有代表性的机制是通过产生转化生长因子（TGF）-β诱导FOXP3 +调节性T细胞（Treg细胞）的诱导，这在人类MSC中也已有报道。最近的研究表明，胰岛素样生长因子（IGF）也参与了FOXP3 + Treg细胞的诱导。我们以前证明了IGF诱导FOXP3 + Treg细胞被IGF结合蛋白4（IGFBP-4）的表达抑制，该蛋白是IGF的抑制剂。由于人类MSC同时产生IGF和IGFBP4，因此可以认为它们通过产生生长因子的正调节Treg细胞以及负调节机制来维持免疫稳态。尽管人间充质干细胞已经用于再生疗法和自身免疫性疾病的治疗中，但对其正负调节机制的控制有望导致更有效的临床应用。