The E3 deubiquitinase USP17 Is a positive regulator of ROR{gamma}t in Th17 cells [Molecular Bases of Disease]

July 28th, 2014 by Han, L., Yang, J., Wang, X., Wu, Q., Yin, S., Li, Z., Zhang, J., Xing, Y., Chen, Z., Tsun, A., Li, D., Piccioni, M., Zhang, Y., Guo, Q., Jiang, L., Bao, L., Lv, L., Li, B.

Stable RORγt expression is pivotal for the development and function of Th17 cells. Here, we demonstrate that expression of the transcription factor RORγt can be regulated through deubiquitination, which prevents proteasome-mediated degradation. We established that USP17 stabilized RORγt protein expression by reducing RORγt polyubiquitination at its K360 residue. In contrast, knockdown of endogenous USP17 in Th17 cells resulted in decreased RORγt protein levels and downregulation of Th17-related genes. Furthermore, USP17 expression was upregulated in CD4+ T cells from systemic lupus erythematosus (SLE) patients. Our data reveal a molecular mechanism in which RORγt expression in Th17 cells can be positively regulated by USP17, thereby modulating Th17 cell functions.