Sheng Feiya, Li Mi, Yu Jia-Mei, Yang Si-Yu, Zou Liang, Yang Guan-Jun, Zhang Le-Le
School of Basic Medical Sciences, Chengdu University, Chengdu, China.
College of Pharmacy, Chengdu University, Chengdu, China.
Front Immunol. 2025 Jan 24;16:1533335. doi: 10.3389/fimmu.2025.1533335. eCollection 2025.
Interleukin-33 (IL-33) is a nuclear factor and member of the IL-1 cytokine family. IL-33 is mainly expressed by epithelial and endothelial cells and exerts its function through interaction with various immune cells, and binding to its receptor can form the IL-33/Suppression of tumorigenicity 2 (ST2) signaling pathway. While most cytokines are actively synthesized within cells, IL-33 is produced passively in response to tissue damage or cell necrosis, indicating its role as a signaling molecule following cellular infection, stress, or trauma. IL-33/ST2 signaling pathway has been proved to play diverse role in the pathological process of central nervous system disorders, cancer, fibrosis, autoimmune diseases, etc. Although research on the IL-33/ST2 signaling pathway has deepened recently, relevant treatment strategies have been proposed, and even targeted drugs are in the preclinical stage; further research on the effect of the IL-33/ST2 signaling pathway in different diseases is still necessary, to provide a clearer understanding of the different roles of IL-33/ST2 in disease progression and to develop new drugs and treatment strategies. Because IL-33/ST2 plays an important role in the occurrence and progression of diseases, the study of therapeutic drugs targeting this pathway is also necessary. This review focused on recent studies on the positive or negative role of IL-33/ST2 in different diseases, as well as the current related drugs targeting IL-33/ST2 in the preclinical and clinical stage. The mechanism of IL-33/ST2 in different diseases and its mediating effect on different immune cells have been summarized, as well as the antibody drugs targeting IL-33 or ST2, natural compounds with a mediating effect, and small molecule substances targeting relative pathway. We aim to provide new ideas and treatment strategies for IL-33/ST2-related drugs to treat different diseases.
白细胞介素-33（IL-33）是一种核因子，属于IL-1细胞因子家族成员。IL-33主要由上皮细胞和内皮细胞表达，并通过与各种免疫细胞相互作用发挥其功能，与其受体结合可形成IL-33/抑瘤素2（ST2）信号通路。虽然大多数细胞因子在细胞内被积极合成，但IL-33是在组织损伤或细胞坏死时被动产生的，这表明它在细胞感染、应激或创伤后作为信号分子发挥作用。IL-33/ST2信号通路已被证明在中枢神经系统疾病、癌症、纤维化、自身免疫性疾病等病理过程中发挥多种作用。尽管最近对IL-33/ST2信号通路的研究有所深入，也提出了相关治疗策略，甚至靶向药物正处于临床前阶段，但仍有必要进一步研究IL-33/ST2信号通路在不同疾病中的作用，以便更清楚地了解IL-33/ST2在疾病进展中的不同作用，并开发新的药物和治疗策略。由于IL-33/ST2在疾病的发生和进展中起重要作用，因此研究针对该通路的治疗药物也很有必要。本综述聚焦于IL-33/ST2在不同疾病中的正向或负向作用的近期研究，以及目前处于临床前和临床阶段的针对IL-33/ST2的相关药物。总结了IL-33/ST2在不同疾病中的作用机制及其对不同免疫细胞的介导作用，以及靶向IL-33或ST2的抗体药物、具有介导作用的天然化合物和靶向相关通路的小分子物质。我们旨在为IL-33/ST2相关药物治疗不同疾病提供新的思路和治疗策略。
