Interleukin-22 in the pathogenesis and potential treatment of liver diseases ☆
Interleukin-22 in the pathogenesis and potential treatment of liver diseases ☆
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DOI：
10.1016/j.livres.2017.09.003
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发表时间：
2017-09
期刊：
影响因子：
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通讯作者：
Shi Yin;D. Feng
中科院分区：
文献类型：
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作者：
Shi Yin;D. Feng
白介素22是白介素10细胞因子家族的一员，在组织修复和宿主防御中发挥重要作用。IL-22与由IL-22R1和IL-10R2组成的异源二聚体受体(R)结合，激活下游信号通路，包括信号转导和转录激活因子3(STAT3)通路。IL-22以STAT3依赖的方式促进生存基因的表达。IL-22R1主要在上皮细胞中表达，而IL-10R2在几乎所有类型的细胞中普遍表达。在肝脏中，IL-22R1表达于肝细胞、肝祖细胞、肝星状细胞和肝癌细胞。IL-22在各种肝损伤模型中保护肝脏，并促进肝损伤后的肝再生。IL-22还通过诱导肝星状细胞衰老来帮助缓解肝纤维化。IL-22被认为是病毒性肝炎的促炎细胞因子，尽管它不直接作用于免疫细胞。据报道，IL-22参与了肝癌的发生和能量代谢的调节。IL-22在肝脏炎症、损伤和修复中的研究将为阐明IL-22作为治疗肝损伤和肝纤维化的潜在候选分子提供有价值的信息。
Interleukin (IL)-22, a member of the IL-10 cytokine family, plays critical roles in tissue repair and host defense. IL-22 binds to its hetereodimeric receptor (R) composed of IL-22R1 and IL-10R2 and activates downstream signaling, including Signal transducer and activator of transcription 3 (STAT3) pathways. IL-22 promotes the expression of survival genes in a STAT3-dependent manner. IL-22R1 expression is restricted mainly in epithelial cells while IL-10R2 is ubiquitously expressed in almost all cell types. In the liver, IL-22R1 is expressed in hepatocytes, liver progenitor cells, hepatic stellate cells and liver cancer cells. IL-22 protects the liver in various liver damage models and promotes liver regeneration after liver injury. IL-22 also helps to resolve liver fibrosis by inducing hepatic stellate cell senescence. IL-22 is considered a pro-inflammatory cytokine in viral hepatitis although it does not directly act on immune cells. IL-22 is reported to be involved in the development of liver cancer and in regulating energy metabolism. Studies on IL-22 in liver inflammation, injury and repair will provide valuable information to clarify IL-22 as a potential candidate for treating liver injury and fibrosis.