Kemp Michael G
Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, OH, USA.
J Cell Death. 2017 Feb 20;9:1179670716685085. doi: 10.1177/1179670716685085. eCollection 2017.
Autoimmune disorders constitute a major and growing health concern. However, the genetic and environmental factors that contribute to or exacerbate disease symptoms remain unclear. Type I interferons (IFNs) are known to break immune tolerance and be elevated in the serum of patients with autoimmune diseases such as lupus. Extensive work over the past decade has characterized the role of a protein termed stimulator of interferon genes, or STING, in mediating IFN expression and activation in response to cytosolic DNA and cyclic dinucleotides. Interestingly, this STING-dependent innate immune pathway both utilizes and is targeted by the cell's autophagic machinery. Given that aberrant interplay between the apoptotic and autophagic machineries contributes to deregulation of the STING-dependent pathway, IFN-regulated autoimmune phenotypes may be influenced by the combined exposure to environmental carcinogens and pathogenic microorganisms and viruses. This review therefore summarizes recent data regarding these important issues in the field of autoimmunity.
自身免疫性疾病是一个日益严重的重大健康问题。然而，导致或加剧疾病症状的遗传和环境因素仍不明确。已知I型干扰素（IFN）会破坏免疫耐受，并在狼疮等自身免疫性疾病患者的血清中升高。过去十年的大量研究已经明确了一种名为干扰素基因刺激因子（STING）的蛋白质在介导对胞质DNA和环二核苷酸的IFN表达和激活中的作用。有趣的是，这种依赖STING的固有免疫途径既利用细胞的自噬机制，又成为其作用靶点。鉴于凋亡和自噬机制之间的异常相互作用会导致依赖STING的途径失调，IFN调节的自身免疫表型可能会受到环境致癌物以及致病微生物和病毒联合暴露的影响。因此，本综述总结了自身免疫领域中有关这些重要问题的最新数据。
