Type I Interferons in the Pathogenesis and Treatment of Autoimmune Diseases
Type I Interferons in the Pathogenesis and Treatment of Autoimmune Diseases
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DOI：
10.1007/s12016-020-08798-2
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发表时间：
2020-06-17
影响因子：
9.1
通讯作者：
Lu, Qianjin
中科院分区：
文献类型：
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作者：
Jiang, Jiao;Zhao, Ming;Lu, Qianjin
I型干扰素（IFN-1）是一组非常重要的细胞因子，由先天免疫细胞产生，但也作用于适应性免疫细胞。IFN-1具有抗病毒、抗肿瘤和抗增殖作用，并且与自身免疫性疾病的起始和维持相关。研究表明，自身免疫性疾病患者的血清或组织中异常表达的IFN-1和/或I型IFN诱导型基因标签与其发病机制、临床表现和疾病活动性相关。具有影响I型IFN信号传导途径的基因突变的I型干扰素病已显示出与系统性红斑狼疮（SLE）相似的症状和特征。此外，在动物模型中的干预和靶向I型IFN信号传导途径的治疗的临床试验都显示出在治疗自身免疫性疾病中的功效。本文就其功能及靶向治疗作一综述IFN-1在成人和儿童自身免疫性疾病中的应用（以及临床试验），所述自身免疫性疾病例如SLE、儿童SLE（pSLE）、类风湿性关节炎（RA）、幼年特发性关节炎（JIA）、幼年皮肌炎（JDM）、舍格伦综合征（SjS）和系统性硬化症（SSc），讨论转录因子和表观遗传修饰的潜在异常调节，并为未来的临床应用提供潜在的发病机制和治疗策略。
Type I interferons (IFN-Is) are a very important group of cytokines that are produced by innate immune cells but also act on adaptive immune cells. IFN-Is possess antiviral, antitumor, and anti-proliferative effects, as well are associated with the initiation and maintenance of autoimmune disorders. Studies have shown that aberrantly expressed IFN-Is and/or type I IFN-inducible gene signatures in the serum or tissues of patients with autoimmune disorders are linked to their pathogenesis, clinical manifestations, and disease activity. Type I interferonopathies with mutations in genes impacting the type I IFN signaling pathway have shown symptoms and characteristics similar to those of systemic lupus erythematosus (SLE). Furthermore, both interventions in animal models and clinical trials of therapies targeting the type I IFN signaling pathway have shown efficacy in the treatment of autoimmune diseases. Our review aims to summarize the functions and targeted therapies (as well as clinical trials) of IFN-Is in both adult and pediatric autoimmune diseases, such as SLE, pediatric SLE (pSLE), rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), juvenile dermatomyositis (JDM), Sjogren syndrome (SjS), and systemic sclerosis (SSc), discussing the potential abnormal regulation of transcription factors and epigenetic modifications and providing a potential mechanism for pathogenesis and therapeutic strategies for future clinical use.