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• W1582114550 abstract "Objective The proinflammatory cytokines tumor necrosis factor α and interleukin‐6 (IL‐6) and the Th17 cell cytokine IL‐17A are implicated in the pathogenesis of rheumatoid arthritis (RA), and the blockade of these cytokines by biologic agents provides clinical benefits for RA patients. We undertook this study to clarify the mechanisms underlying the efficacy of IL‐6 blockade in RA and to find a novel target for treatment of RA. Methods We examined gene expression profiles of CD4+ T cells by DNA microarray analysis before and after treatment with an anti–IL‐6 receptor antibody, tocilizumab (TCZ), in RA patients who exhibited good clinical responses to the treatment. Using murine CD4+ T cells, we then examined the roles of a newly identified molecule whose expression was significantly reduced in CD4+ T cells by TCZ therapy. We also examined the effect of the forced expression of the molecule on retinoic acid receptor–related orphan nuclear receptor γt (RORγt)–induced IL‐17A production in CD4+ T cells and on RORγt‐induced IL‐17A promoter activation. Results We identified AT‐rich–interactive domain– containing protein 5A (ARID‐5A) as a new molecule down‐regulated by IL‐6 blockade in the form of TCZ therapy. IL‐6 induced the expression of ARID‐5A in CD4+ T cells during Th17 cell differentiation by a STAT‐3–dependent mechanism, whereas IL‐6–induced ARID‐5A expression was not affected by the absence of RORγt, a lineage‐specifying transcription factor of Th17 cells. Furthermore, ARID‐5A physically associated with RORγt through its N‐terminal region and inhibited RORγt‐induced Th17 cell differentiation. Conclusion ARID‐5A is a lineage‐specific attenuator of Th17 cell differentiation and may be involved in the pathogenesis of RA." @default.
• W1582114550 created "2016-06-24" @default.
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• W1582114550 date "2014-04-28" @default.
• W1582114550 modified "2023-10-13" @default.
• W1582114550 title "AT-Rich-Interactive Domain-Containing Protein 5A Functions as a Negative Regulator of Retinoic Acid Receptor-Related Orphan Nuclear Receptor γt-Induced Th17 Cell Differentiation" @default.
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• W1582114550 doi "https://doi.org/10.1002/art.38324" @default.
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