Hui Lu, Chen Xiaolin, Huang Mengke, Jiang Yongmei, Liu Ting
Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, No. 20, Section 3, Renmin Road South, Chengdu 610041, China.
Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Sichuan University, Chengdu 610041, China.
Int J Mol Sci. 2025 Feb 24;26(5):1941. doi: 10.3390/ijms26051941.
TANK-binding kinase 1 (TBK1) is a key signaling kinase involved in innate immune and inflammatory responses. TBK1 drives immune cells to participate in the inflammatory response by activating the NF-κB and interferon regulatory factor signaling pathways in immune cells, promoting the expression of pro-inflammatory genes, and regulating immune cell function. Thus, it plays a crucial role in initiating a signaling cascade that establishes an inflammatory environment. In inflammation-related diseases, TBK1 acts as a bridge linking inflammation to immunity, metabolism, or tumorigenesis, playing an important role in the pathogenesis of immune-mediated inflammatory diseases, metabolic, inflammatory syndromes, and inflammation-associated cancers by regulating the activation of inflammatory pathways and the production of inflammatory cytokines in cells. In this review, we focused on the mechanisms of TBK1 in immune cells and inflammatory-related diseases, providing new insights for further studies targeting TBK1 as a potential treatment for inflammation-related diseases. Thus, optimizing and investigating highly selective cell-specific TBK1 inhibitors is important for their application in these diseases.
TANK结合激酶1(TBK1)是一种参与先天免疫和炎症反应的关键信号激酶。TBK1通过激活免疫细胞中的核因子κB(NF-κB)和干扰素调节因子信号通路,驱动免疫细胞参与炎症反应,促进促炎基因的表达,并调节免疫细胞功能。因此,它在启动建立炎症环境的信号级联反应中起着至关重要的作用。在炎症相关疾病中,TBK1作为连接炎症与免疫、代谢或肿瘤发生的桥梁,通过调节细胞内炎症信号通路的激活和炎症细胞因子的产生,在免疫介导的炎症性疾病、代谢性炎症综合征和炎症相关癌症的发病机制中发挥重要作用。在这篇综述中,我们重点关注了TBK1在免疫细胞和炎症相关疾病中的作用机制,为进一步以TBK1为靶点治疗炎症相关疾病的研究提供了新的见解。因此,优化和研究高选择性细胞特异性TBK1抑制剂对其在这些疾病中的应用具有重要意义。