{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T03:29:33Z","timestamp":1792553373183,"version":"4.5.0"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2015,5,1]],"date-time":"2015-05-01T00:00:00Z","timestamp":1430438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>ROR\u03b3t is a key transcription factor that controls the development and function of inflammatory Th17. The mechanisms that regulate ROR\u03b3t stability remain unclear. We report that Th17 cells highly express the deubiquitinase ubiquitin-specific protease (USP)4, which is essential for maintaining ROR\u03b3t 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 ROR\u03b3t, thereby promoting ROR\u03b3t function and IL-17A transcription. Interestingly, TGF-\u03b2 plus IL-6 enhanced USP4-mediated deubiquitination of ROR\u03b3t. Moreover, USP4 and IL-17 mRNA, but not ROR\u03b3t 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.<\/jats:p>","DOI":"10.4049\/jimmunol.1401451","type":"journal-article","created":{"date-parts":[[2015,3,28]],"date-time":"2015-03-28T10:45:39Z","timestamp":1427539539000},"page":"4094-4097","source":"Crossref","is-referenced-by-count":78,"title":["Cutting Edge: Ubiquitin-Specific Protease 4 Promotes Th17 Cell Function under Inflammation by Deubiquitinating and Stabilizing ROR\u03b3t"],"prefix":"10.1093","volume":"194","author":[{"given":"Jing","family":"Yang","sequence":"first","affiliation":[{"name":"Key Laboratory of Molecular Virology and Immunology, Unit of Molecular Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai 200025 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, The First Affiliated Hospital of Anhui Medical University , Hefei 230032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Han","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Huashan Hospital, Fudan University , Shanghai 200040 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixiang","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, The First Affiliated Hospital of Anhui Medical University , Hefei 230032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuwen","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Huashan Hospital, Fudan University , Shanghai 200040 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuojia","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Virology and Immunology, Unit of Molecular Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai 200025 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Nie","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Virology and Immunology, Unit of Molecular Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai 200025 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuying","family":"Yin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Virology and Immunology, Unit of Molecular Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai 200025 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