Cutting edge: Ubiquitin-specific protease 4 promotes Th17 cell function under inflammation by deubiquitinating and stabilizing RORγt.

نویسندگان

  • Jing Yang
  • Peng Xu
  • Lei Han
  • Zhixiang Guo
  • Xiuwen Wang
  • Zuojia Chen
  • Jia Nie
  • Shuying Yin
  • Miranda Piccioni
  • Andy Tsun
  • Ling Lv
  • Shenglin Ge
  • Bin Li
چکیده

RORγt is a key transcription factor that controls the development and function of inflammatory Th17. The mechanisms that regulate RORγt stability remain unclear. We report that Th17 cells highly express the deubiquitinase ubiquitin-specific protease (USP)4, which is essential for maintaining RORγt and Th17 cell function. Inhibition of the catalytic activity of USP4 with vialinin A, a compound derived from Chinese traditional medicine, dampened Th17 differentiation. USP4 interacted and deubiquitinated K48-linked polyubiquitination of RORγt, thereby promoting RORγt function and IL-17A transcription. Interestingly, TGF-β plus IL-6 enhanced USP4-mediated deubiquitination of RORγt. Moreover, USP4 and IL-17 mRNA, but not RORγt mRNA, were significantly elevated in CD4(+) T cells from patients with rheumatic heart disease. Thus, USP4 could be a novel therapeutic target for the treatment of Th17-modulated autoimmune diseases.

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عنوان ژورنال:
  • Journal of immunology

دوره 194 9  شماره 

صفحات  -

تاریخ انتشار 2015