Zhang Wencan, Cao Xu
Shanghai Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China.
Shanghai Frontiers Science Center for Drug Target Identification and Delivery, and the Engineering Research Center of Cell and Therapeutic Antibody of the Ministry of Education, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai, China.
Front Immunol. 2025 Jan 8;15:1515715. doi: 10.3389/fimmu.2024.1515715. eCollection 2024.
Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) are integral to T cell biology, influencing immune responses and associated diseases. This review explores the interplay between the UPR and T cell immunity, highlighting the role of these cellular processes in T cell activation, differentiation, and function. The UPR, mediated by IRE1, PERK, and ATF6, is crucial for maintaining ER homeostasis and supporting T cell survival under stress. However, the precise mechanisms by which ER stress and the UPR regulate T cell-mediated immunity remain incompletely understood. Emerging evidence suggests that the UPR may be a potential therapeutic target for diseases characterized by T cell dysfunction, such as autoimmune disorders and cancer. Further research is needed to elucidate the complex interactions between ER stress, the UPR, and T cell immunity to develop novel therapeutic strategies for T cell-associated diseases.
内质网(ER)应激和未折叠蛋白反应(UPR)是T细胞生物学不可或缺的一部分,影响免疫反应及相关疾病。本综述探讨了UPR与T细胞免疫之间的相互作用,强调了这些细胞过程在T细胞活化、分化和功能中的作用。由肌醇需求酶1(IRE1)、蛋白激酶样内质网激酶(PERK)和活化转录因子6(ATF6)介导的UPR对于维持内质网稳态以及在应激状态下支持T细胞存活至关重要。然而,内质网应激和UPR调节T细胞介导的免疫的确切机制仍未完全清楚。新出现的证据表明,UPR可能是治疗以T细胞功能障碍为特征的疾病(如自身免疫性疾病和癌症)的潜在治疗靶点。需要进一步研究来阐明内质网应激、UPR和T细胞免疫之间的复杂相互作用,以开发针对T细胞相关疾病的新型治疗策略。