Su Huiting, Na Ning, Zhang Xiaodong, Zhao Yong
Transplantation Biology Research Division, State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beichen West Road 1-5, Chaoyang District, Beijing, 100101, China.
University of Chinese Academy of Sciences, Beijing, China.
Inflamm Res. 2017 Mar;66(3):209-216. doi: 10.1007/s00011-016-0995-1. Epub 2016 Oct 17.
CD74 (MHC class II invariant chain, Ii) is a non-polymorphic type II transmembrane glycoprotein. It is clear that, in addition to be an MHC class II chaperone, CD74 has a diversity of biological functions in physiological and pathological situations. CD74 also participates in other non-MHC II protein trafficking, such as angiotensin II type I receptor. In addition, CD74 is a cell membrane high-affinity receptor for macrophage migration inhibitory factor (MIF), D-dopachrome tautomerase (D-DT/MIF-2) and bacterial proteins. CD74 also regulates T-cell and B-cell developments, dendritic cell (DC) motility, macrophage inflammation, and thymic selection. The activation of receptor complex CD74/CD44 may lead to multiple intracellular signal pathways, such as the activation of the extracellular signal regulated kinase (ERK) 1 and 2, the PI3K-Akt signal transduction cascade, NFκB, and the AMP-activated protein kinase (AMPK) pathway. CD74 plays important roles in many inflammatory diseases, such as liver fibrosis, type I diabetes, systemic lupus erythematosus, and Alzheimer disease. In this study, we will focus on the immunological functions of CD74 molecules and its roles in immune-relevant disorders.
CD74(主要组织相容性复合体II类恒定链,Ii)是一种非多态性的II型跨膜糖蛋白。很明显,除了作为主要组织相容性复合体II类分子伴侣外,CD74在生理和病理情况下还具有多种生物学功能。CD74还参与其他非主要组织相容性复合体II类蛋白的转运,如血管紧张素II 1型受体。此外,CD74是巨噬细胞迁移抑制因子(MIF)、D-多巴色素互变异构酶(D-DT/MIF-2)和细菌蛋白的细胞膜高亲和力受体。CD74还调节T细胞和B细胞的发育、树突状细胞(DC)的运动、巨噬细胞炎症和胸腺选择。受体复合物CD74/CD44的激活可能导致多种细胞内信号通路,如细胞外信号调节激酶(ERK)1和2的激活、PI3K-Akt信号转导级联、NFκB和AMP激活的蛋白激酶(AMPK)通路。CD74在许多炎症性疾病中发挥重要作用,如肝纤维化、I型糖尿病、系统性红斑狼疮和阿尔茨海默病。在本研究中,我们将重点关注CD74分子的免疫功能及其在免疫相关疾病中的作用。