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The role of Hobit in Trm differentiation was investigated through targeted silencing experiments. Psmb5 expression regulation was explored by identifying BRD2 as a key transcription factor, with the interaction validated through chromatin immunoprecipitation\u2010quantitative polymerase chain reaction. The impact of BRD2 succinylation on Trm differentiation was examined by manipulating succinyl\u2010CoA levels in T cells. Humanized NSG chimeras representing synovitis provided insights into Trm infiltration in RA synovitis and were used for translational experiments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In patients with RA, a notable predisposition of CD4<jats:sup>+<\/jats:sup> T cells toward differentiation into Trm cells was observed, demonstrating a positive correlation with the disease activity score 28. Remarkably, Hobit was a pivotal facilitator in the formation of RA CD4<jats:sup>+<\/jats:sup> Trm cells. Mechanistic studies unveiled the dysregulation of proteasomal Psmb5 in T cells of patients with RA as the key factor contributing to elevated Hobit protein levels. The deficiency of proteasomal Psmb5 was intricately linked to BRD2, with succinylation exerting a significant impact on Psmb5 transcription and Trm cell differentiation. This heightened BRD2 succinylation was attributed to elevated levels of mitochondrial succinyl\u2010CoA in RA T cells. Consequently, targeting succinyl\u2010CoA within CD4<jats:sup>+<\/jats:sup> T cells controlled the inflammation of synovial tissues in humanized chimeras.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Mitochondrial succinyl\u2010CoA fosters the succinylation of BRD2, resulting in compromised transcription of proteasomal Psmb5 and the differentiation of Trm cells in RA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42954","type":"journal-article","created":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T08:41:00Z","timestamp":1721637660000},"page":"1743-1757","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Mitochondrial Control of Proteasomal Psmb5 Drives the Differentiation of Tissue\u2010Resident Memory T Cells in Patients with Rheumatoid Arthritis"],"prefix":"10.1002","volume":"76","author":[{"given":"Tong","family":"Wu","sequence":"first","affiliation":[{"name":"Soochow University  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