The genetics and biology of Irf5-mediated signaling in lupus
The genetics and biology of Irf5-mediated signaling in lupus
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DOI：
10.1080/08916930701510905
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发表时间：
2007-01-01
期刊：
影响因子：
3.5
通讯作者：
Alarcon-Riquelme, Marta E.
中科院分区：
文献类型：
--
作者：
Kozyrev, Sergey V.;Alarcon-Riquelme, Marta E.
最近，I 型干扰素途径在自身免疫性疾病系统性红斑狼疮 (SLE) 的发生和发展中的重要性引起了人们的广泛关注。许多 SLE 患者的血清 IFN-α 水平升高，并表现出 IFN 基因表达“特征”，其特征是白细胞和靶组织中 IFN 反应基因的强烈过度表达。此外，约 20% 接受 IFN-α 治疗的癌症患者表现出类似 SLE 的症状，有些患者后来发展为该疾病。 IFN-α 通路的关键基因之一 IRF5 被发现与 SLE 密切相关。两个功能性 SNP 导致选择性剪接并改变 IRF5 基因表达的稳态水平。此外，该基因在外显子6中存在多态性插入/缺失，这有助于IRF5亚型模式的多样性。有趣的是，最近的研究尚未发现IRF5与其他自身免疫性疾病（例如类风湿性关节炎或牛皮癣）之间的关联，这表明IRF5在狼疮的发展中具有独特的作用。在这里，我们介绍了 IRF5 遗传学及其生物学功能的最新知识，并讨论了 IRF5 导致 SLE 易感性的可能方式。
Recently much attention was attracted to the importance of the type I interferon pathway in the initiation and development of the autoimmune disease systemic lupus erythematosus (SLE). Many SLE patients have increased serum levels of IFN-alpha and display an IFN gene expression "signature" characterized by strong overexpression of IFN-responsive genes in leukocytes and target tissues. Moreover, about 20% of cancer patients treated with IFN-alpha therapy manifest symptoms resembling SLE and some later develop the disease. One of the key genes of the IFN-alpha pathway, IRF5, was found to be strongly associated with SLE. Two functional SNPs lead to alternative splicing and altered steady-state level of IRF5 gene expression. Besides, the gene has a polymorphic inserion/deletion in exon 6, which contributes to the diversity in the isoform pattern of IRF5. Interestingly, recent studies have not found association of IRF5 with the other autoimmune diseases, such as rheumatoid arthritis or psoriasis, suggesting the unique role for IRF5 in the development of lupus. Here, we present the current knowledge on IRF5 genetics and its biological function and discuss the possible ways in which IRF5 contributes to susceptibility to SLE.