Epithelial–immune interactions in lung immunity: regulation, reprogramming, and therapeutic targeting in pulmonary disease

Spanning the airways and alveoli, epithelial cells form a dynamic sensory interface that continuously samples the inhaled environment and communicates with resident and recruited immune cells to maintain lung homeostasis. This bidirectional crosstalk, mediated by cytokines, lipid mediators, pattern recognition signaling, and direct cell-cell contact, is essential for coordinating host defense against pathogens while preventing collateral tissue damage. Disruptions to this finely balanced circuit underlie a broad spectrum of pulmonary diseases, from asthma and chronic obstructive pulmonary disease (COPD) to cystic fibrosis and lung cancer. Understanding how epithelial and immune compartments interact, and how those interactions break down under pathological conditions, is therefore central to advancing both fundamental lung biology and clinical therapeutics.Despite considerable progress in characterizing individual cell types, the field lacks a unified mechanistic framework that captures how epithelial–immune circuits are established, maintained, and ultimately subverted in disease. Chronic infection, persistent inflammation, and environmental exposures, including cigarette smoke, pollutants, and microbial dysbiosis, can reprogram epithelial identity and immune tone in ways that sustain dysfunction long after the initial insult. Emerging single-cell technologies, organoid models, and spatially resolved transcriptomics are now revealing the molecular logic of these interactions at unprecedented resolution, while parallel advances in immunomodulatory antimicrobials, biologics, and host-directed therapies are translating mechanistic insights into clinical opportunities.This Research Topic aims to consolidate these advances into a cohesive, cross-disciplinary resource. By bringing together work that spans barrier biology, innate and adaptive immunity, chronic infection, and inflammation-driven pathology, the collection will define shared principles governing epithelial–immune dysfunction and highlight the most promising avenues for therapeutic intervention across pulmonary disease contexts.We welcome Original Research, Review, Mini Review, and Perspective articles addressing epithelial–immune interactions in the context of pulmonary health and disease. Relevant themes include, but are not limited to:- Epithelial barrier regulation and its role in lung immune homeostasis- Innate immune sensing by airway epithelial cells, including pattern recognition and cytokine crosstalk- Adaptive immune modulation shaped by epithelial-derived signals- Chronic infection and biofilm persistence, particularly in cystic fibrosis and bronchiectasis- Epithelial–immune reprogramming driven by environmental exposures, smoking, or repeated inflammatory insults- Disease-specific pathogenesis in asthma, COPD, cystic fibrosis, and lung cancer- Immunomodulatory and host-directed therapeutic strategies, including novel antimicrobials and biologicsStudies using in vitro, in vivo, or patient-derived models are equally encouraged, provided they offer clear mechanistic or translational insight. Topic editors: Y. Peter Di, Renat Shaykhiev Source: https://www.frontiersin.org/research-topics/82930/epithelial-immune-interactions-in-lung-immunity-regulation-reprogramming-and-therapeutic-targeting-in-pulmonary-disease