CD226分子的信号转导通路及功能研究进展

Research progress in signal transduction pathway and function of CD226 molecule

CD226分子属于免疫球蛋白超家族成员,广泛表达于T细胞、自然杀伤(NK)细胞、单核细胞、巨噬细胞等细胞表面。CD226胞外结构域与配体CD155、CD112结合后,激活细胞膜内侧的Src家族激酶Fyn、Src等,进而活化下游PI3K-AKT和VAV-1-ERK通路,调控T细胞的分化、增殖和细胞因子分泌,增强CD8^(+)T细胞、NK细胞的杀伤功能。CD226胞内结构域的S329位点磷酸化后结合淋巴细胞功能相关抗原1,协同促进T细胞、NK细胞免疫突触的形成。临床疾病相关研究发现,CD226促进抗肿瘤免疫应答,CD226^(+)CD8^(+)T细胞的存在是免疫检查点阻断治疗有效的前提。此外,CD226参与1型糖尿病、系统性红斑狼疮等自身免疫性疾病的发生和发展。深入理解CD226信号转导机制及其介导的功能,可为靶向CD226的肿瘤免疫治疗和自身免疫性疾病治疗提供坚实的理论基础。

CD226 molecule is a member of the immunoglobulin superfamily and is widely expressed on the surface of T cells,natural killer(NK)cells,monocytes,macrophages and other cells.After binding with ligands CD155 and CD112,CD226 extracellular domain activates Src family kinases Fyn and Src on the inner side of cell membrane,and then activates downstream PI3K-AKT and VAV-1-ERK pathways,regulates the differentiation,proliferation,and cytokine secretion of T cells,and enhances cytotoxicity of CD8^(+)T cells and NK cells.Phosphorylated intracellular CD226 S329 binds to lymphocyte function-associated antigen-1 and synergistically promotes the formation of immune synapses in T cells and NK cells.Clinical disease-related studies have found that CD226 promotes anti-tumor immune responses,and the presence of CD226^(+)CD8^(+)T cells is a prerequisite for effective immune checkpoint blockade therapy.In addition,CD226 is involved in the occurrence and development of autoimmune diseases such as type I diabetes and systemic lupus erythematosus.A deep understanding of CD226 signal transduction mechanism and its mediated functions can provide a solid theoretical basis for CD226-targeted immunotherapy of tumors and autoimmune diseases.