糖皮质激素诱导的肿瘤坏死因子受体相关蛋白及其配体在肝脏疾病中的作用

Research advances in the role of the glucocorticoid-induced tumor necrosis factor receptor-related protein and its ligand in liver diseases

糖皮质激素诱导的肿瘤坏死因子受体(GITR)属于肿瘤坏死因子受体家族,与其特异性配体GITRL结合后,所介导的下游信号既可以作为协同刺激分子,促进效应T淋巴细胞增殖与细胞因子分泌;还可以影响调节性T淋巴细胞增殖和抑制效应T淋巴细胞的功能,从而调控效应T淋巴细胞的炎症反应与杀伤肿瘤细胞的作用。GITRL主要表达于抗原递呈细胞且有胞内结构域,与GITR结合后,可以通过受体/配体逆向信号从而影响抗原递呈细胞的功能。在肝脏疾病中,GITRL/GITR信号不仅与肝移植术后和基因治疗中免疫排异反应有关,也与肿瘤免疫微环境形成、肿瘤的免疫逃逸有关。GITRL/GITR在其他肝脏疾病发生和进展中的作用仍有待进一步研究。

Glucocorticoid-induced tumor necrosis factor receptor(GITR)is a member of the tumor necrosis factor receptor superfamily,and after it specifically binds to GITR ligand(GITRL),the downstream signals mediated by them can not only serve as a costimulatory molecule to promote the proliferation and cytokine secretion of effector T cells,but also affect the proliferation of regulatory T cells and inhibit the function of effector T cells,thereby regulating the inflammatory response and tumor cell-killing effect of effector T cells.GITRL is mainly expressed in antigen-presenting cells and has an intracellular domain,and the binding of GITRL to GITR can affect the function of antigen-presenting cells via receptor/ligand reverse signaling.In liver diseases,GITRL/GITR signal is not only involved in immune rejection after liver transplantation and gene therapy,but also associated with the formation of tumor immune microenvironment and the immune escape of tumor.Further studies are needed to explore the role of GITRL/GITR in the development and progression of other liver diseases.