USP12 promotes CD4+ T cell responses through deubiquitinating and stabilizing BCL10 |
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| Authors: | 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 |
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| Affiliation: | 1.Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China ;2.Department of Emergency Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China ;3.Department of Biotherapy, Sun Yat-Sen University Cancer Center, Guangzhou, China ;4.State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China |
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| 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.Subject terms: Ubiquitins, T cells |
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