gpi锚定的LY6/uPAR家族蛋白在连接膜微域与免疫调节和疾病中的作用

IF 5.6 2区医学 Q1 HEMATOLOGY

Critical reviews in oncology/hematology Pub Date : 2025-09-26 DOI:10.1016/j.critrevonc.2025.104971

Jingyi Wen , Le Wu , Shangwei Zhong , Hanguo Shan , Jun-Li Luo

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引用次数: 0

摘要

糖基磷脂酰肌醇（GPI）锚定的LY6/uPAR家族蛋白是结构保守但功能多样的免疫信号调节因子。LY6A、LY6C、LY6E、LY6G、CD59、PSCA和uPAR等成员由一个特征性的三指LY6/uPAR （LU）结构域和优先定位于脂质筏，它们协调必要的免疫过程，包括T细胞和B细胞活化、树突状细胞成熟、中性粒细胞和自然杀伤（NK）细胞反应以及巨噬细胞极化。这些蛋白在癌症、传染病、自身免疫性疾病和神经炎症的发病机制中有越来越多的作用。GPI锚定促进了受体的预定向、纳米簇的形成和膜微域内的快速信号转导，从而实现了免疫信号的精确时空控制。一些LY6/uPAR成员已经成为有希望的临床靶点，其翻译策略包括CAR-T细胞疗法、抗体-药物偶联物和脂质筏调节剂。这篇综述对当前的知识进行了全面的概述，将LY6/uPAR蛋白的结构、空间和功能特征与它们在健康和疾病中的相关性联系起来，确定了关键的未解决的机制问题，并强调了在精确免疫学背景下出现的转化机会。

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The role of GPI-anchored LY6/uPAR family proteins in connecting membrane microdomains with immune regulation and diseases

Glycosylphosphatidylinositol (GPI)-anchored LY6/uPAR family proteins are structurally conserved yet functionally diverse regulators of immune signaling. Defined by a characteristic three-finger LY6/uPAR (LU) domain and preferential localization to lipid rafts, members such as LY6A, LY6C, LY6E, LY6G, CD59, PSCA, and uPAR orchestrate essential immune processes, including T and B cell activation, dendritic cell maturation, neutrophil and natural killer (NK) cell responses, and macrophage polarization. These proteins are increasingly implicated in the pathogenesis of cancer, infectious diseases, autoimmune disorders, and neuroinflammation. GPI anchoring facilitates receptor pre-orientation, nanocluster formation, and rapid signal transduction within membrane microdomains, thereby enabling precise spatial and temporal control of immune signaling. Several LY6/uPAR members have emerged as promising clinical targets, with translational strategies encompassing CAR-T cell therapies, antibody–drug conjugates, and lipid raft–modulating agents. This review presents a comprehensive overview of current knowledge, linking the structural, spatial, and functional characteristics of LY6/uPAR proteins to their relevance in health and disease, identifying key unresolved mechanistic questions, and underscoring emerging translational opportunities within the context of precision immunology.

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来源期刊

Critical reviews in oncology/hematology 医学-血液学

CiteScore

11.00

自引率

3.20%

发文量

213

审稿时长

55 days

期刊介绍： Critical Reviews in Oncology/Hematology publishes scholarly, critical reviews in all fields of oncology and hematology written by experts from around the world. Critical Reviews in Oncology/Hematology is the Official Journal of the European School of Oncology (ESO) and the International Society of Liquid Biopsy.