Autophagic checks and balances of cellular immune responses.
Autophagic checks and balances of cellular immune responses.
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DOI：
10.1080/27694127.2022.2058677
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发表时间：
2022
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中科院分区：
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IRF 3（干扰素调节因子3）是抗病毒先天免疫应答的关键组分。IRF 3缺陷在病毒感染期间对宿主造成有害影响。IRF 3功能失调与病毒性、炎症性和肝脏疾病相关。IRF 3的转录活性和促凋亡活性均参与了乙醇和高脂饮食诱导的肝损伤中炎症和凋亡的加剧。因此，IRF 3活性的调节具有后果，并且它是感染性和炎性疾病的潜在治疗靶点。我们最近发现，IRF 3可被小分子金诺芬通过激活细胞宏自噬/自噬途径降解。自噬是一种分解代谢途径，有助于细胞内稳态和抗病毒宿主防御。通过自噬降解IRF 3可能是病毒使用的一种新策略。此外，IRF 3功能在其他疾病中也是有害的，包括肝损伤和细菌感染。更好地理解自噬在调节IRF 3功能中的作用对开发治疗策略具有重要意义。因此，自噬在先天免疫反应中提供了制衡。
IRF3 (interferon regulatory factor 3) is a critical component of the antiviral innate immune response. IRF3 deficiency causes detrimental effects to the host during virus infection. Dysregulation of IRF3 functions is associated with viral, inflammatory, and hepatic diseases. Both transcriptional and pro-apoptotic activities of IRF3 are involved in the exacerbated inflammation and apoptosis in liver injury induced by ethanol and high-fat diets. Therefore, regulation of IRF3 activities has consequences, and it is a potential therapeutic target for infectious and inflammatory diseases. We recently revealed that IRF3 is degraded by a small molecule, auranofin, by activating the cellular macroautophagy/autophagy pathway. Autophagy is a catabolic pathway that contributes to cellular homeostasis and antiviral host defense. Degradation of IRF3 by autophagy may be a novel strategy used by the viruses to their benefit. In addition, IRF3 functions are harmful in other diseases, including liver injury and bacterial infection. A better understanding of the role of autophagy in regulating IRF3 functions has significant implications in developing therapeutic strategies. Therefore, autophagy provides checks and balances in the innate immune response.