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 tissue-specific redistribution of IL-17A and the therapeutic benefit of its neutralization suggest that IL-17A may serve as a clinically actionable target in patients with overlapping asthma and colitis. The study also shows that IL-17A plays a reciprocal role in influencing immune responses in both lung and gut.
Keywords: IL-17A; asthma; colitis; inflammation; lung-gut axis.
© 2025 Wu et al.