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溶酶体跨膜蛋白5:对免疫细胞功能的影响及对免疫相关缺陷的意义

Lysosomal transmembrane protein 5: Impact on immune cell function and implications for immune-related deficiencies.

作者信息

Sun Peng-Peng, Liao Shi-Xia, Sang Peng, Liu Mao-Mao, Yang Ji-Bin

机构信息

Department of Orthopedics Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China.

Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, China.

出版信息

Heliyon. 2024 Aug 22;10(17):e36705. doi: 10.1016/j.heliyon.2024.e36705. eCollection 2024 Sep 15.

Abstract

Lysosomal transmembrane protein 5 (LAPTM5) is a lysosomal-associated protein that interacts with surface receptors on various immune cells, including B cells, T cells, macrophages and dendritic cells. Dysregulated expression of LAPTM5 is implicated in the development of multiple immune system-related diseases. In the context of tumors, elevated LAPTM5 levels in immune cells are associated with decreased cell membrane levels of T cell receptors (TCR) or B cell receptors (BCR), leading to impaired antigen presentation and immune escape, thereby promoting tumor progression. Besides, LAPTM5 is critical for inducing non-apoptotic cell death in tumor parenchymal cells since its downregulation leads to inhibition of the cell death pathway in the tumor parenchyma and subsequent enhanced tumorigenesis. LAPTM5 also affects the cell cycle as the elevated LAPTM5 expression in solid tumors causes its inability to block the G0/G1 stage. In non-solid tumors, abnormal LAPTM5 expression disrupts blood cell development and causes irregular proliferation. Furthermore, in the nervous system, aberrant LAPTM5 expression in microglia is correlated with Alzheimer's disease severity. In this context, further preclinical research is essential to validate LAPTM5 as a potential target for diagnosis, therapy, and prognosis in immune-related disorders and tumors. This review summarized the current insights into LAPTM5's role in tumors and immune-related deficits, highlighting its potential as a valuable biomarker and therapeutic target.

摘要

溶酶体跨膜蛋白5(LAPTM5)是一种与溶酶体相关的蛋白,可与包括B细胞、T细胞、巨噬细胞和树突状细胞在内的多种免疫细胞表面受体相互作用。LAPTM5表达失调与多种免疫系统相关疾病的发生有关。在肿瘤背景下,免疫细胞中LAPTM5水平升高与T细胞受体(TCR)或B细胞受体(BCR)的细胞膜水平降低有关,导致抗原呈递受损和免疫逃逸,从而促进肿瘤进展。此外,LAPTM5对诱导肿瘤实质细胞的非凋亡性细胞死亡至关重要,因为其下调会导致肿瘤实质细胞死亡途径受到抑制,进而增强肿瘤发生。LAPTM5还影响细胞周期,因为实体瘤中LAPTM5表达升高会导致其无法阻断G0/G1期。在非实体瘤中,LAPTM5异常表达会破坏血细胞发育并导致异常增殖。此外,在神经系统中,小胶质细胞中LAPTM5异常表达与阿尔茨海默病严重程度相关。在此背景下,进一步的临床前研究对于验证LAPTM5作为免疫相关疾病和肿瘤诊断、治疗及预后的潜在靶点至关重要。本综述总结了目前对LAPTM5在肿瘤和免疫相关缺陷中作用的认识,突出了其作为有价值生物标志物和治疗靶点的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b12c/11401081/47237dc8e108/gr1.jpg

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