IRF5 Acts as a Potential Therapeutic Marker in Inflammatory Bowel Diseases
IRF5 Acts as a Potential Therapeutic Marker in Inflammatory Bowel Diseases
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IRF5 作为炎症性肠病的潜在治疗标志物
DOI：
10.1093/ibd/izaa200
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发表时间：
2021-03-01
影响因子：
4.9
通讯作者：
Zhou，Guangxi
中科院分区：
文献类型：
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作者：
Yang，Yonghong;Zhang，Cui;Zhou，Guangxi
炎症性肠病(IBDS)是一种慢性炎症性疾病，包括溃疡性结肠炎(UC)和克罗恩病(CD)。众所周知，干扰素调节因子(IRF)5与多种炎症性疾病的发病密切相关。方法采用免疫组织化学、免疫印迹和实时定量聚合酶链式反应检测IBD患者外周血单个核细胞(PBMC)和炎性粘膜中IRF5的表达。结果活动期IBD患者PBMC和炎性结肠组织中IRF5的表达明显增加，且与疾病活动程度显著相关。异位过表达IRF5可通过调节T-bet和RAR相关的孤儿受体C，促进IBD患者CD4+T细胞向Th1和Th17细胞分化，而下调IRF5的作用则相反。肿瘤坏死因子α可上调CD+T细胞中IRF5的表达，但英夫利昔单抗可显著降低CD患者CD+T细胞和肠粘膜中IRF5的表达。结论本研究揭示了IBD患者IRF5水平与疾病活动性相关的新机制，并可能通过调节Th1、Th17免疫应答和细胞因子的产生，为IBD的治疗提供可能的指标。
BackgroundInflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn’s disease (CD), are chronic inflammatory disorders. As is well known, interferon regulatory factor (IRF) 5 is closely associated with the pathogenesis of various inflammatory diseases. But the exact role of IRF5 in IBD remains unclear.MethodsIn this study, we detected IRF5 expression in peripheral blood mononuclear cells (PBMCs) and inflamed mucosa from IBD patients by immunohistochemistry, western blot, and quantitative real-time polymerase chain reaction. Peripheral blood CD4+T cells were stimulated with inflammatory cytokines and transfected by lentivirus.ResultsIn active IBD patients, the expression of IRF5 in PBMCs and inflamed colonic tissues was obviously increased and significantly associated with disease activity. Ectopic overexpression of IRF5 could promote the differentiation of IBD CD4+T cells into Th1 and Th17 cells by regulating T-bet and RAR related orphan receptor C, whereas knockdown of IRF5 had the opposite effects. Tumor necrosis factor (TNF)-α upregulated expression of IRF5 in CD4+T cells, but anti-TNF treatment with infliximab could markedly reduce IRF5 expression in CD4+T cells and intestinal mucosa of CD patients.ConclusionOur study reveals a novel mechanism that IRF5 levels are correlated with disease activity in IBD and might function as a possible marker for the management of IBD via regulating Th1 and Th17 immune responses and cytokine production.