Deubiquitinases as pivotal regulators of T cell functions

Abstract

T cells efficiently respond to foreign antigens to mediate immune responses against infections but are tolerant to self-tissues. Defect in T cell activation is associated with severe immune deficiencies, whereas aberrant T cell activation contributes to the pathogenesis of diverse autoimmune and inflammatory diseases. An emerging mechanism that regulates T cell activation and tolerance is ubiquitination, a reversible process of protein modification that is counter-regulated by ubiquitinating enzymes and deubiquitinases (DUBs). DUBs are isopeptidases that cleave polyubiquitin chains and remove ubiquitin from target proteins, thereby controlling the magnitude and duration of ubiquitin signaling. It is now well recognized that DUBs are crucial regulators of T cell responses and serve as potential therapeutic targets for manipulating immune responses in the treatment of immunological disorders and cancer. This review will discuss the recent progresses regarding the functions of DUBs in T cells.

Keywords

deubiquitinase / ubiquitination / T cell activation / T cell differentiation / T cell tolerance

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Acknowledgements

Work performed in the authors’ laboratories is supported by grants from the US National Institutes of Health (Nos. AI057555, AI064639, GM84459, and AI104519; Shao-Cong Sun) and the National Natural Science Foundation of China (Nos.31570770 and 31770818; Xiao-Dong Yang).

Compliance with ethics guidelines

Xiao-Dong Yang and Shao-Cong Sun declare no conflict of interest. This is a review article and does not involve a research protocol.

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