Liu Xingyue, Li Ya, Wu Wenwen, Huang Han, Hao Yanmei, Song Chuanwang
Anhui Province Key Laboratory of Immunology in Chronic Diseases, Bengbu Medical University, Bengbu, Anhui, China.
School of Laboratory Medicine, Bengbu Medical University, Bengbu, Anhui, China.
Front Immunol. 2025 Sep 5;16:1650972. doi: 10.3389/fimmu.2025.1650972. eCollection 2025.
Th9 cells, a distinct subset of T helper cells, are defined by their production of IL-9. Th9 cells play a role in the development of various diseases by participating in mucosal immune responses, defending tissue barriers, and regulating inflammatory responses. For instance, Th9 cells contribute to inflammatory bowel disease by secreting IL-9, which damages the intestinal epithelial barrier. The effects mediated by Th9-derived IL-9 exhibit environment-dependent characteristics. In allergic asthma, IL-9 drives inflammation, while in specific tumor microenvironments, IL-9 can exert anti-tumor effects. Th9 cell differentiation is governed by a complex, multi-layered regulatory network. This network centers on the synergistic action of transforming growth factor-beta (TGF-β) and interleukin-4 (IL-4). Additionally, it involves multiple other mechanisms. These include exogenous signals such as IL-2 and IL-35; intrinsic transcription factors like the ATF-like protein BATF and PU.1; epigenetic modifications, including histone acetylation and DNA methylation; and metabolic reprogramming, such as glycolysis and lipid metabolism, among others. This review systematically summarizes the regulatory mechanisms governing Th9 cell differentiation. It elucidates these mechanisms and reveals potential therapeutic targets, including transcription factors such as PU.1, IRF4, and BATF. This work paves the way for the development of Th9-related immunotherapies.
Th9细胞是辅助性T细胞的一个独特亚群，由其产生的白细胞介素-9（IL-9）所定义。Th9细胞通过参与黏膜免疫反应、保卫组织屏障和调节炎症反应，在多种疾病的发展过程中发挥作用。例如，Th9细胞通过分泌IL-9促进炎症性肠病，IL-9会破坏肠道上皮屏障。Th9细胞衍生的IL-9介导的效应具有环境依赖性特征。在过敏性哮喘中，IL-9会引发炎症，而在特定的肿瘤微环境中，IL-9可发挥抗肿瘤作用。Th9细胞的分化受一个复杂的、多层的调控网络支配。这个网络以转化生长因子-β（TGF-β）和白细胞介素-4（IL-4）的协同作用为中心。此外，它还涉及多种其他机制。这些机制包括外源性信号，如IL-2和IL-35；内在转录因子，如ATF样蛋白BATF和PU.1；表观遗传修饰，包括组蛋白乙酰化和DNA甲基化；以及代谢重编程，如糖酵解和脂质代谢等。本综述系统地总结了调控Th9细胞分化的机制。它阐明了这些机制，并揭示了潜在的治疗靶点，包括PU.1、IRF4和BATF等转录因子。这项工作为Th9相关免疫疗法的开发铺平了道路。
