Li Heng, Zhang Yongliang, Peh Hong Yong
Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117456, Singapore; NUSMED Immunology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore 117456, Singapore.
Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117456, Singapore; NUSMED Immunology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore 117456, Singapore.
Semin Immunol. 2025 Jun;78:101948. doi: 10.1016/j.smim.2025.101948. Epub 2025 Mar 28.
Interferon regulatory factor 3 (IRF3) is a transcription factor known primarily for its role in antiviral immunity via regulation of type I interferons (IFNs). Recent research has broadened its significance to encompass metabolic disorders, particularly obesity and diabetes. Obesity is characterized by chronic low-grade inflammation, insulin resistance, and metabolic dysfunction, all of which are increasingly found to be associated with immune signaling pathways. IRF3 has emerged as an important regulator in the development of obesity and type 2 diabetes (T2D), predominantly through its regulation of inflammatory cytokines production in various cells in adipose tissue. In obese individuals, IRF3 is activated in the adipocytes and adipose tissue macrophages, to promote the expression of inflammatory cytokines, thereby contributing to chronic inflammation and exacerbating insulin resistance. Moreover, IRF3 has been linked to mitochondrial dysfunction in hepatic disorders, further amplifying metabolic stress and imbalances associated with obesity. The growing evidence suggests that IRF3 is an important mediator in both immune and metabolic pathways, highlighting its potential as a target for the development of therapeutic interventions for obesity-related inflammation and metabolic dysfunction.
干扰素调节因子3（IRF3）是一种转录因子，主要因其通过调节I型干扰素（IFN）在抗病毒免疫中的作用而闻名。最近的研究扩大了其重要性，将其涵盖范围扩展到代谢紊乱，特别是肥胖和糖尿病。肥胖的特征是慢性低度炎症、胰岛素抵抗和代谢功能障碍，所有这些都越来越多地被发现与免疫信号通路有关。IRF3已成为肥胖和2型糖尿病（T2D）发展中的重要调节因子，主要是通过其对脂肪组织中各种细胞炎症细胞因子产生的调节。在肥胖个体中，IRF3在脂肪细胞和脂肪组织巨噬细胞中被激活，以促进炎症细胞因子的表达，从而导致慢性炎症并加剧胰岛素抵抗。此外，IRF3与肝脏疾病中的线粒体功能障碍有关，进一步加剧了与肥胖相关的代谢应激和失衡。越来越多的证据表明，IRF3是免疫和代谢途径中的重要介质，突出了其作为肥胖相关炎症和代谢功能障碍治疗干预靶点的潜力。
