Interleukin (IL)‐1 receptor antagonist (IL‐1Ra), a naturally occurring antagonist of IL‐1α/IL‐1β signaling pathways, has been attributed to the immunosuppressive effects of mesenchymal stem cells (MSCs). MSCs, in IL‐1Ra‐dependent manner, suppressed production of IL‐1β in dermal macrophages, induced their polarization in anti‐inflammatory M2 phenotype, attenuated antigen‐presenting properties of dendritic cells (DCs), and promoted expansion of immunosuppressive T regulatory cells in the skin, which resulted in enhanced repair of the nonhealing wounds. Reduced activation of inflammasome and suppressed production of IL‐1β in macrophages were mainly responsible for beneficial effects of MSC‐derived IL‐1Ra in alleviation of acute lung injury, dry eye syndrome, and corneal injury. Through the production of IL‐1Ra, MSCs reduced migration of DCs to the draining lymph nodes and attenuated generation of inflammatory Th1 and Th17 cells that resulted in alleviation of fulminant hepatitis and rheumatoid arthritis. MSCs, in IL‐1Ra‐dependent manner, reduced liver fibrosis by suppressing production of Type I collagen in hepatic stellate cells. IL‐1Ra was, at least partially, responsible for enhanced proliferation of hepatocytes and chondrocytes in MSC‐treated animals with partial hepatectomy and osteoarthritis. Despite of these beneficial effects, IL‐1Ra‐dependent inhibition of IL‐1α/IL‐1β‐signaling significantly increased risk of infections. Therefore, future experimental and clinical studies should delineate potential side effects of MSC‐derived IL‐1Ra before IL‐1Ra‐overexpressing MSCs could be used as a potentially new therapeutic agent for the treatment of acute and chronic inflammatory diseases.

中文翻译：

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白介素1受体拮抗剂在基于间充质干细胞的组织修复和再生中的作用。

白介素（IL）-1受体拮抗剂（IL-1Ra）是IL-1α/IL-1β信号传导途径的天然拮抗剂，被认为是间充质干细胞（MSC）的免疫抑制作用。MSC以IL-1Ra依赖性方式抑制真皮巨噬细胞中IL-1β的产生，诱导其在抗炎M2表型中的极化，减弱树突状细胞（DC）的抗原呈递特性，并促进免疫抑制T调节细胞的扩增在皮肤上，这导致不愈合伤口的修复得到增强。炎性体的激活减少和巨噬细胞中IL-1β的产生受到抑制，这主要是由MSC衍生的IL-1Ra减轻急性肺损伤，干眼症和角膜损伤的有益作用。通过生产IL-1Ra，MSC减少了DCs向引流淋巴结的迁移，并减弱了炎症性Th1和Th17细胞的产生，从而减轻了暴发性肝炎和类风湿性关节炎。MSC以IL-1Ra依赖性方式通过抑制肝星状细胞中I型胶原蛋白的产生来减少肝纤维化。IL-1Ra至少部分负责增强经部分肝切除和骨关节炎的MSC治疗动物的肝细胞和软骨细胞的增殖。尽管具有这些有益效果，但IL-1Ra依赖的IL-1α/IL-1β信号转导抑制作用显着增加了感染风险。因此，