Unfolded protein responses in T cell immunity

Wencan Zhang; Xu Cao

doi:10.3389/fimmu.2024.1515715

Unfolded protein responses in T cell immunity

Front Immunol. 2025 Jan 8:15:1515715. doi: 10.3389/fimmu.2024.1515715. eCollection 2024.

Authors

Wencan Zhang¹, Xu Cao²

Affiliations

¹ Shanghai Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China.
² 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.

Abstract

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.

Keywords: T cell activation; T cell differentiation; endoplasmic reticulum stress; immune regulation; unfolded protein response.

Publication types

Review

MeSH terms

Animals
Autoimmune Diseases / immunology
Endoplasmic Reticulum Stress* / immunology
Humans
Lymphocyte Activation / immunology
Neoplasms / immunology
Neoplasms / therapy
Signal Transduction / immunology
T-Lymphocytes* / immunology
T-Lymphocytes* / metabolism
Unfolded Protein Response* / immunology

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was funded by National Natural Science Foundation of China (82373892, 82471776) and the startup funding from Shanghai Jiao Tong University.