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

作者：Fu, Yuling; Wang, Peng; Zhao, Jingjing; Tan, Yunke; Sheng, Junli; He, Shitong; Du, Xialin; Huang, Yulan; Yang, Yalong; Li, Jinling; Cai, Yuxiong; Liu, Yuxuan; Hu, Shengfeng^*

来源：Cell Death and Differentiation, 2021, 28(10): 2857-2870.

DOI：10.1038/s41418-021-00787-y

• KAPPA-B ACTIVATION
• REGULATING INNATE IMMUNITY
• PHOSPHORYLATION
• SYSTEM
• GROWTH
• MALT1

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-kappa B 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.

• 单位
  中山大学; 南方医科大学