Krausz Ludovic Tibor, Bianchini Rodolfo, Ronchetti Simona, Fettucciari Katia, Nocentini Giuseppe, Riccardi Carlo
Dipartimento di Medicina Clinica e Sperimentale, Sezione di Farmacologia, Tossicologia e Chemioterapia, Università di Perugia, Perugia, Italy.
ScientificWorldJournal. 2007 May 1;7:533-66. doi: 10.1100/tsw.2007.106.
Glucocorticoid-induced TNFR-Related (GITR) protein is a member of the tumor necrosis factor receptor superfamily that modulates acquired and natural immune response. It is expressed in several cells and tissues, including T cells, natural killer cells, and, at lower levels, in cells of innate immunity. GITR is activated by its ligand, GITRL, mainly expressed on antigen presenting and endothelial cells. Recent evidence suggests that the GITR/GITRL system participates in the development of inflammatory responses, including shock, either due to early response of neutrophils and macrophages, or together with autoimmune/allergic pathogenesis. The pro-inflammatory role of the GITR/GITRL system is due to: 1) modulation of the extravasation process, 2) activation of innate immunity cells, 3) activation of effector T cells also favored by partial inhibition of suppressor T cells and modulation of dendritic function. This review summarizes the in vivo role of the GITR/GITRL system in inflammation and shock, explaining the mechanisms responsible for their effects, considering the interplay among the different cells of the immune system and transduction pathways activated by GITR and GITRL triggering. The hidden aspects about GITR/GITRL function, crucial for treatment planning of inflammatory diseases and shock by modulation of this system is stressed.
糖皮质激素诱导的肿瘤坏死因子受体相关（GITR）蛋白是肿瘤坏死因子受体超家族的成员，可调节获得性免疫和天然免疫反应。它在多种细胞和组织中表达，包括T细胞、自然杀伤细胞，以及在先天免疫细胞中低水平表达。GITR由其配体GITRL激活，GITRL主要表达于抗原呈递细胞和内皮细胞。最近的证据表明，GITR/GITRL系统参与炎症反应的发生发展，包括休克，这要么是由于中性粒细胞和巨噬细胞的早期反应，要么是与自身免疫/过敏发病机制共同作用的结果。GITR/GITRL系统的促炎作用归因于：1）调节渗出过程；2）激活先天免疫细胞；3）通过部分抑制抑制性T细胞和调节树突状细胞功能，促进效应T细胞的激活。本综述总结了GITR/GITRL系统在炎症和休克中的体内作用，解释了其作用机制，考虑了免疫系统不同细胞之间的相互作用以及GITR和GITRL触发激活的信号转导途径。强调了GITR/GITRL功能中隐藏的方面，这对于通过调节该系统来治疗炎症性疾病和休克至关重要。
