Innate Immune Circuits in Lung Disease: Myeloid Cells, ILCs, and Tissue-Driven Inflammation

The lung hosts a diverse repertoire of innate immune cells positioned at mucosal interfaces where environmental exposures meet host defense. Alveolar macrophages, interstitial macrophage subsets, dendritic cells, and innate lymphoid cells (ILCs) coordinate sentinel, inflammatory, and tissue-repair functions. In many lung diseases, dysregulation of these populations drives chronic inflammation or fibrosis through altered metabolic states, cytokine signaling, pathogen sensing, or epithelial crosstalk.Recent advances in single-cell RNA-seq, spatial transcriptomics, and in vivo lineage tracing have uncovered previously unrecognized heterogeneity and plasticity within lung innate immune lineages. These technologies now allow detailed mapping of disease-associated states and communication hubs, opening opportunities for therapeutic targeting. This Research Topic will consolidate state-of-the-art discoveries in this fast-evolving field.Lung diseases remain a major global health challenge, with inflammatory and autoimmune components contributing to tissue damage, impaired gas exchange, and chronic remodeling. Increasing evidence demonstrates that innate immune cells, particularly macrophage subsets and group 2 innate lymphoid cells (ILC2s), serve as central orchestrators of inflammatory, reparative, and maladaptive responses. Yet, their interactions with epithelial cells, stromal cells, and adaptive immunity remain incompletely understood across different pulmonary conditions.This Research Topic aims to bring together cutting-edge studies defining how innate immune circuits initiate, amplify, or restrain inflammation in lung diseases, including asthma, idiopathic pulmonary fibrosis, COPD, acute lung injury, viral pneumonitis, and autoimmune lung disorders. By integrating mechanistic immunology, single-cell/spatial transcriptomics, translational models, and therapeutic insights, this collection will highlight emerging paradigms and identify molecular targets for intervention.Our goal is to build a unified framework describing how myeloid cells, ILCs, and related innate populations contribute to pulmonary pathology and recovery, ultimately guiding new diagnostics and immunotherapies.We are interested in contributions that investigate innate immune mechanisms underlying lung disease. Areas of interest include, but are not limited to: • Dendritic cell and macrophage subset specialization in airway and parenchymal inflammation • ILC activation, plasticity, and interactions with macrophages and epithelial cells • Innate immune drivers of fibrosis, airway remodeling, or mucous metaplasia • Innate responses to infection and sterile injury • Metabolic reprogramming of myeloid cells and ILCs in pulmonary disease • Insights from single-cell, spatial, or multi-omics profiling • Crosstalk between innate and adaptive immunity in lung pathology • Translational or therapeutic approaches modulating innate immunityOriginal Research, Reviews/Mini-reviews, Perspectives, Brief Reports, Methods, and Clinical Translational Studies are all welcomed. Topic editors: Xin Li, Yoshihiro Sakano, Venkata Ramireddy Narala Source: https://www.frontiersin.org/research-topics/77486/innate-immune-circuits-in-lung-disease-myeloid-cells-ilcs-and-tissue-driven-inflammation