Crosstalk between airway epithelial cells and mast cells in airway inflammation

Respir Res. 2025 Nov 5;26(1):310. doi: 10.1186/s12931-025-03388-2.

Abstract

Airway epithelial cells (AECs) and mast cells (MCs) are pivotal initiators and amplifiers of airway inflammation, orchestrating a dynamic crosstalk that drives pathological hyperreactivity in respiratory diseases. AECs, as the frontline barrier, detect pathogens and allergens, releasing cytokines (e.g., IL-33, TSLP) and chemokines to activate neighboring MCs. Conversely, MC-derived proteases (tryptase, chymase) and mediators (histamine, leukotrienes) disrupt epithelial junctions (e.g., E-cadherin, occludin), exacerbating barrier dysfunction and perpetuating cycles of inflammation. This reciprocal interaction establishes a molecular hub for 'hyperinflammation' in asthma, chronic obstructive pulmonary disease (COPD), and viral infections, while also contributing to pathological processes such as airway remodeling, fibrosis, and epithelial-mesenchymal transition (EMT). Therefore, elucidating the synergistic mechanisms underlying AEC-MC crosstalk is critically important. This review synthesizes emerging insights into AEC-MC crosstalk, emphasizing context-specific mechanisms in viral, allergic, and chronic inflammatory settings, and provide suggestions for future research directions.

Keywords: Airway epithelial cells; Airway inflammation; Crosstalk; Mast cells.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Communication* / physiology
  • Epithelial Cells* / immunology
  • Epithelial Cells* / metabolism
  • Epithelial Cells* / pathology
  • Humans
  • Inflammation / immunology
  • Inflammation / metabolism
  • Inflammation / pathology
  • Inflammation Mediators / metabolism
  • Mast Cells* / immunology
  • Mast Cells* / metabolism
  • Mast Cells* / pathology
  • Respiratory Mucosa* / immunology
  • Respiratory Mucosa* / metabolism
  • Respiratory Mucosa* / pathology

Substances

  • Inflammation Mediators