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

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.

Automated summary

USP12 is identified as a critical regulator of CD4(+) T cell activation, promoting the phenotype and signaling of these cells. While USP12-deficient CD4(+) T cells protect mice from autoimmune diseases, they attenuate immune responses against bacterial infections.