Pan L, Chen Z, Wang L, Chen C, Li D, Wan H, Li B, Shi G

The T-box transcriptional factor T-bet is crucial in the development, differentiation and function of Th1 cells. It drives the Th1 immune response primarily through promoting expression of Th1 hallmark cytokine IFN-γ. Although T-bet was found associated with many immune-mediated diseases such as asthma and systemic sclerosis, little is known about ...

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the regulation of T-bet stability and function. Here we identified USP10, a carboxyl-terminal ubiquitin-processing protease, interacts with T-bet in the nucleus. Overexpression of USP10 directly inhibited T-bet ubiquitination and increased the expression of T-bet. We further confirmed Quercetin, a reported inhibitor of T-bet, could target USP10. Quercetin treatment downregulated USP10 and promoted T-bet degradation in a proteasome dependent way. Moreover, we found USP10 expression was upregulated in asthmatic patient PBMC, suggesting USP10 may maintain high level of T-bet and IFN-γ to fight against Th2-dominated inflammation.

Date: May. 17, 2014

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