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of CD4+ T cell transcription factor genes including T-bet, GATA binding protein 3 (GATA)-3, related orphan receptor C (RORC) and forkhead box protein 3 (FOXP3) are associated with acute anterior uveitis either in the presence or absence of ankylosing spondylitis (AAU+AS+; AAU+AS-). METHODS: The study included 676 patients with AAU, including 298 patients with AAU+AS+, 378 patients with AAU+AS-, and 596 unrelated healthy controls in a Chinese Han population. Copy number variations were examined by real-time PCR. RESULTS: The frequency of a high copy number (CN) of T-bet was increased in AAU+AS+ as well as AAU+AS- patients when compared with controls (P value after Bonferroni correction [P(corr)] = 4.3 x 10(-5); odds ratio [OR] = 2.0 and P(corr) = 1.2 x 10(-8); OR = 2.3, respectively). The frequency of a high CN of GATA-3 was significantly higher in AAU+AS+ patients than in controls (P(corr) = 1.8 x 10(-7); OR = 4.9). A higher frequency of CN of FOXP3 was found in female AAU+AS+ patients and female AAU+AS- patients (P(corr) = 0.005, OR = 5.9 and P(corr) = 0.004, OR = 4.9, respectively ). No association was found between CNVs of RORC and AAU+AS- or AAU+AS+ patients. CONCLUSIONS: A high copy number of T-bet and GATA-3 confers susceptibility to AAU and AS, and a high copy number of FOXP3 confers susceptibility to female patients with AAU either with or without AS.

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he pathogenesis of psoriasis. The small molecule bromodomain and extraterminal domain (BET) inhibitors, that disrupt interaction of BET proteins with acetylated histones have recently demonstrated efficacy in various models of inflammation through suppression of several pathways, one of them being synthesis of IL-17A/IL-22 which primarily depends on transcription factor, retinoic acid receptor-related orphan receptor C (RORC). However, the efficacy and mechanistic aspect of a BET inhibitor in mouse model of skin inflammation has not been explored previously. Therefore, this study investigated the role of BET inhibitor, JQ-1 in mouse model of psoriasis-like inflammation. Mice were topically applied imiquimod (IMQ) to develop psoriasis-like inflammation on the shaved back and ear followed by assessment of skin inflammation (myeloperoxidase activity, ear thickness, and histopathology), RORC and its signature cytokines (IL-17A/IL-22). JQ-1 suppressed IMQ-induced skin inflammation as reflected by a decrease in ear thickness/myeloperoxidase activity, and RORC/IL-17A/IL-22 expression. Additionally, a RORalpha/gamma agonist SR1078 was utilized to investigate the role of RORC in BET-mediated skin inflammation. SR1078 reversed the protective effect of JQ-1 on skin inflammation at both histological and molecular levels in the IMQ model. The current study suggests that BET bromodomains are involved in psoriasis-like inflammation through induction of RORC/IL-17A pathway. Therefore, inhibition of BET bromodomains may provide a new therapy against skin inflammation.