Journal
CELL DEATH AND DIFFERENTIATION
Volume 28, Issue 10, Pages 2857-2870Publisher
SPRINGERNATURE
DOI: 10.1038/s41418-021-00787-y
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Funding
- National Natural Science Foundation of China [81901614, 32070906, 81971805, 81501137, 81402560]
- Guangdong Natural Science Foundation [2019A1515011103, 2020A1515010158]
- Guangzhou Science and Technology Research Project [201804010061]
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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.
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.
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