IL-17A as a Key Mediator of Pulmonary-Intestinal Immune Interactions in a Mouse Model of Asthma and Colitis

作者：Chengyong Wu, X Hu, Zhongyuan Mo, Yan Meng, Yingying Du, Yunyu Duan, Zaopin Zeng, Jiahui Shan, Juan Li, Nali Zhang, Youfeng Ma, Huaqi Wang, Chi Liu, Guojun Zhang, Paul S. Foster, Huisha Xu, Fuguang Li, Ming Yang · 发表于：Journal of Inflammation Research · 年份：2025 · DOI：10.2147/jir.s512605 · 被引用次数：4 · 研究领域：Psoriasis: Treatment and Pathogenesis、Asthma and respiratory diseases、Dermatology and Skin Diseases

Background: The immunological interaction between the lung and gut remains underexplored, particularly in the context of coexisting mucosal inflammation. While IL-17A has been implicated in both asthma and colitis independently, its role in coordinating systemic immune responses across tissue compartments is not well defined. Methods: In this study, we developed a combined house dust mite-induced asthma model and dextran sulfate sodium-induced colitis model to investigate the role of IL-17A in driving inflammation in both the lungs and the intestines. Results: Our findings demonstrate that IL-17A neutralization markedly reduced airway and intestinal inflammation, attenuated mucus hypersecretion, downregulated pro-inflammatory cytokine expression, and alleviated colitis severity. Histopathological analysis revealed decreased infiltration of immune cells, including eosinophils, lymphocytes, and macrophages, in both the lungs and colonic tissues following IL-17A blockade. Additionally, we observed a reduction in mucus production, particularly in the airways, highlighting IL-17A's direct role in mucin regulation. Transcriptomic analysis confirmed that IL-17A blockade downregulated several immune-related pathways in colon tissues, further supporting its central role in mediating multi-organ inflammation. Conclusion: These findings indicate that IL-17A represents a systemic immunomodulator, which orchestrates compartmentalized immune responses along the lung-gut axis. The observed ...