School of Medicine, Royal College of Surgeons in Ireland, Medical University of Bahrain, Busaiteen, Bahrain.
AdventHealth Orlando Family Medicine, Orlando, FL, USA.
Nat Rev Endocrinol. 2024 Oct;20(10):573-587. doi: 10.1038/s41574-024-00990-0. Epub 2024 May 20.
Interferon regulatory factors (IRFs) comprise a family of nine transcription factors in mammals. IRFs exert broad effects on almost all aspects of immunity but are best known for their role in the antiviral response. Over the past two decades, IRFs have been implicated in metabolic physiology and pathophysiology, partly as a result of their known functions in immune cells, but also because of direct actions in adipocytes, hepatocytes, myocytes and neurons. This Review focuses predominantly on IRF3 and IRF4, which have been the subject of the most intense investigation in this area. IRF3 is located in the cytosol and undergoes activation and nuclear translocation in response to various signals, including stimulation of Toll-like receptors, RIG-I-like receptors and the cGAS-STING pathways. IRF3 promotes weight gain, primarily by inhibiting adipose thermogenesis, and also induces inflammation and insulin resistance using both weight-dependent and weight-independent mechanisms. IRF4, meanwhile, is generally pro-thermogenic and anti-inflammatory and has profound effects on lipogenesis and lipolysis. Finally, new data are emerging on the role of other IRF family members in metabolic homeostasis. Taken together, data indicate that IRFs serve as critical yet underappreciated integrators of metabolic and inflammatory stress.
干扰素调节因子（IRFs）是哺乳动物中一类包含九个转录因子的家族。IRFs 对几乎所有免疫方面都有广泛的影响，但它们在抗病毒反应中的作用最为人所知。在过去的二十年中，IRFs 已被牵涉到代谢生理学和病理生理学中，部分原因是它们在免疫细胞中的已知功能，但也因为它们在脂肪细胞、肝细胞、肌细胞和神经元中的直接作用。本综述主要关注 IRF3 和 IRF4，这两个因子是该领域研究最多的因子。IRF3 位于细胞质中，在各种信号的刺激下发生激活和核易位，包括 Toll 样受体、RIG-I 样受体和 cGAS-STING 途径的刺激。IRF3 通过抑制脂肪组织的产热来促进体重增加，并且还通过依赖体重和不依赖体重的机制诱导炎症和胰岛素抵抗。同时，IRF4 通常具有产热和抗炎作用，并对脂肪生成和脂肪分解有深远影响。最后，关于其他 IRF 家族成员在代谢稳态中的作用的新数据正在出现。总之，数据表明，IRFs 是代谢和炎症应激的关键但未被充分认识的整合因子。
