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CD74在免疫疾病中的生物学功能及意义。

The biological function and significance of CD74 in immune diseases.

作者信息

Su Huiting, Na Ning, Zhang Xiaodong, Zhao Yong

机构信息

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.

出版信息

Inflamm Res. 2017 Mar;66(3):209-216. doi: 10.1007/s00011-016-0995-1. Epub 2016 Oct 17.

Abstract

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.

摘要

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。

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