Abstract |
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.
|
Authors | 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 |
Journal | Journal of immunology (Baltimore, Md. : 1950)
(J Immunol)
Vol. 194
Issue 9
Pg. 4094-7
(May 01 2015)
ISSN: 1550-6606 [Electronic] United States |
PMID | 25821221
(Publication Type: Journal Article)
|
Copyright | Copyright © 2015 by The American Association of Immunologists, Inc. |
Chemical References |
- Interleukin-17
- Nuclear Receptor Subfamily 1, Group F, Member 3
- RNA, Messenger
- RORC protein, human
- USP4 protein, human
- Ubiquitin Thiolesterase
- Ubiquitin-Specific Proteases
|
Topics |
- Cell Differentiation
- Humans
- Inflammation
(genetics, immunology, metabolism, pathology)
- Interleukin-17
(genetics, immunology)
- Nuclear Receptor Subfamily 1, Group F, Member 3
(chemistry, genetics, metabolism)
- RNA, Messenger
(genetics)
- Rheumatic Heart Disease
(genetics, immunology, pathology)
- Th17 Cells
(immunology, metabolism)
- Ubiquitin Thiolesterase
(genetics, metabolism)
- Ubiquitin-Specific Proteases
- Ubiquitination
|