Wottawa Felix, Bordoni Dora, Baran Nathan, Rosenstiel Philip, Aden Konrad
Institute of Clinical Molecular Biology, Christian-Albrechts-University and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Department of Internal Medicine I., Christian-Albrechts-University and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Eur J Immunol. 2021 Apr;51(4):785-797. doi: 10.1002/eji.202048777. Epub 2021 Mar 12.
The gastrointestinal tract is a highly complex microenvironment under constant interaction with potentially harmful pathogens. Inflammatory bowel disease (IBD) is an archetypical inflammatory disease, in which the intestinal epithelium, defective autophagy, endoplasmic reticulum stress and dysbiosis play a key role. Although no risk-mediating gene variants of STING (TMEM173) have been identified so far, several seminal findings have elucidated a novel understanding of STING in the context of acute and chronic inflammation. STING, an endoplasmic reticulum resident adaptor protein binding cyclic dinucleotides, is a main inducer of type I interferons and canonically involved in antiviral and antibacterial immunity. Recent research has shed light on additional features of STING signaling involved in regulating the microbiota, facilitating autophagy, cell death or ER stress. Importantly, an increasing amount of studies suggests a considerable overlap of IBD pathophysiology and features of STING signaling. Since compelling evidence shows dysregulated type I IFNs in IBD, it is prompting to speculate on the hypothetical role of cGAS/STING/type I IFN signaling in IBD. Here, we summarize recent findings about the origin and function of STING signaling in the gastrointestinal tract and evolve the hypothesis that disturbed STING signaling might be profoundly interconnected with the pathophysiology of IBD.
胃肠道是一个高度复杂的微环境，不断与潜在有害病原体相互作用。炎症性肠病（IBD）是一种典型的炎症性疾病，其中肠道上皮、自噬缺陷、内质网应激和微生物群失调起着关键作用。尽管迄今为止尚未鉴定出STING（TMEM173）的风险介导基因变异，但一些重要发现阐明了在急性和慢性炎症背景下对STING的新认识。STING是一种结合环状二核苷酸的内质网驻留衔接蛋白，是I型干扰素的主要诱导剂，通常参与抗病毒和抗菌免疫。最近的研究揭示了STING信号传导在调节微生物群、促进自噬、细胞死亡或内质网应激方面的其他特征。重要的是，越来越多的研究表明IBD病理生理学与STING信号传导特征存在相当大的重叠。由于有力证据表明IBD中I型干扰素失调，因此推测cGAS/STING/I型干扰素信号传导在IBD中的假设作用很有意义。在此，我们总结了关于胃肠道中STING信号传导的起源和功能的最新发现，并提出了一个假设，即紊乱的STING信号传导可能与IBD的病理生理学密切相关。
