Mucosal surfaces serve as critical battlegrounds where the immune system must balance tolerance to commensal organisms with rapid defense against pathogens. Myeloid cells encompassing both granulocytes (neutrophils, eosinophils, mast cells, basophils) and mononuclear phagocytes (macrophages, monocytes, dendritic cells) orchestrate this delicate equilibrium through diverse effector and regulatory functions. Recent single-cell and spatial profiling studies have unveiled remarkable heterogeneity within each myeloid lineage, revealing specialized subsets with distinct developmental origins, tissue niches, and functional programs. Neutrophils provide frontline antimicrobial defense while shaping adaptive immunity through neutrophil extracellular traps and cytokine networks. Eosinophils and mast cells drive type 2 inflammation in allergic diseases, yet also contribute to tissue homeostasis and repair. Macrophages and dendritic cells integrate signals from epithelium, microbiome, and stromal cells to determine inflammatory versus tolerogenic outcomes. Understanding how these myeloid populations interact and collectively shape mucosal immunity is essential for developing targeted therapies for inflammatory bowel disease, asthma, chronic infections, and cancer.
This Research Topic aims to provide a comprehensive framework for understanding how diverse myeloid cell populations collaborate to maintain mucosal barrier integrity and how their dysregulation drives disease. Despite advances in characterizing individual myeloid subsets, critical knowledge gaps persist regarding: (1) functional crosstalk between granulocytes and mononuclear phagocytes during inflammation and resolution; (2) tissue-specific programming of myeloid cells across intestinal, respiratory, and urogenital mucosae; (3) metabolic and epigenetic mechanisms governing myeloid plasticity and trained immunity; and (4) translational strategies to selectively modulate pathogenic versus protective myeloid functions. We seek contributions that elucidate molecular circuits controlling neutrophil recruitment and NETosis, eosinophil and mast cell degranulation and mediator release, macrophage polarization and tissue remodeling, and dendritic cell antigen presentation at mucosal sites. Emerging therapeutic approaches, including biologics targeting type 2 cytokines, nanomedicine for selective myeloid reprogramming, trained immunity vaccines, and cell-based therapies, demonstrate proof-of-concept efficacy in preclinical models. This Research Topic will bridge mechanistic immunology with translational innovation, fostering the development of next-generation myeloid-directed interventions that restore mucosal homeostasis while preserving protective immunity.
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