USP12 promotes CD4+ T cell responses through deubiquitinating and stabilizing BCL10

作者：Yuling Fu, Peng Wang, Jingjing Zhao, Yunke Tan, Junli Sheng, Shitong He, Xialin Du, Yulan Huang, Yalong Yang, Jinling Li, Yuxiong Cai, Yuxuan Liu, Shengfeng Hu · 发表于：Cell Death and Differentiation · 年份：2021 · DOI：10.1038/s41418-021-00787-y · 被引用次数：21 · 研究领域：Ubiquitin and proteasome pathways、NF-κB Signaling Pathways、Autophagy in Disease and Therapy

Abstract Deubiquitinases (DUBs) regulate diverse biological processes and represent a novel class of drug targets. However, the biological function of only a small fraction of DUBs, especially in adaptive immune response regulation, is well-defined. In this study, we identified DUB ubiquitin-specific peptidase 12 (USP12) as a critical regulator of CD4 + T cell activation. USP12 plays an intrinsic role in promoting the CD4 + T cell phenotype, including differentiation, activation, and proliferation. Although USP12-deficient CD4 + T cells protected mice from autoimmune diseases, the immune response against bacterial infection was subdued. USP12 stabilized B cell lymphoma/leukemia 10 (BCL10) by deubiquitinating, and thereby activated the NF-κB signaling pathway. Interestingly, this USP12 regulatory mechanism was identified in CD4 + T cells, but not in CD8 + T cells. Our study results showed that USP12 activated CD4 + T cell signaling, and targeting USP12 might help develop therapeutic interventions for treating inflammatory diseases or pathogen infections.