Aryl hydrocarbon receptor antagonism and its role in rheumatoid arthritis.
Aryl hydrocarbon receptor antagonism and its role in rheumatoid arthritis.
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DOI：
10.2147/jep.s63549
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发表时间：
2015
影响因子：
--
通讯作者：
Kishimoto T
中科院分区：
文献类型：
--
作者：
Nguyen NT;Nakahama T;Nguyen CH;Tran TT;Le VS;Chu HH;Kishimoto T
虽然类风湿性关节炎（RA）是最常见的自身免疫性疾病，影响全球约1%的人口，但其致病机制知之甚少。烟草烟雾是类风湿关节炎的环境危险因素，含有多种芳香烃受体（Ahr）配体，也称为二恶英受体。AHR在免疫系统中起着关键作用。我们先前证明辅助性T细胞中的Ahr有助于胶原诱导的关节炎（RA的小鼠模型）的发展。其他研究表明，香烟烟雾冷凝物和纯Ahr配体通过改变骨代谢和诱导成纤维细胞样滑膜细胞中的促炎反应而加重RA。与这些发现相一致，一些Ahr拮抗剂如α-萘酚酮、白藜芦醇和GNF 351逆转了Ahr配体在RA发病机制中的作用。在这篇综述中，我们总结了Ahr在免疫系统中的功能和Ahr拮抗剂治疗RA的潜在临床益处的当前知识。
Although rheumatoid arthritis (RA) is the most common autoimmune disease, affecting approximately 1% of the population worldwide, its pathogenic mechanisms are poorly understood. Tobacco smoke, an environmental risk factor for RA, contains several ligands of aryl hydrocarbon receptor (Ahr), also known as dioxin receptor. Ahr plays critical roles in the immune system. We previously demonstrated that Ahr in helper T-cells contributes to development of collagen-induced arthritis, a mouse model of RA. Other studies have shown that cigarette smoke condensate and pure Ahr ligands exacerbate RA by altering bone metabolism and inducing proinflammatory responses in fibroblast-like synoviocytes. Consistent with these findings, several Ahr antagonists such as α-naphthoflavone, resveratrol, and GNF351 reverse the effect of Ahr ligands in RA pathogenesis. In this review, we summarize the current knowledge of Ahr function in the immune system and the potential clinical benefits of Ahr antagonism in treating RA.