Mast Cell Dynamics in Asthmatic Inflammation

Mast cells are central effectors in asthma, acting as both initiators and amplifiers of airway inflammation. Residing in peribronchial tissues and the epithelium, they respond to immunoglobulin E (IgE) crosslinking and non-IgE stimuli by releasing preformed granule mediators (histamine, tryptase, chymase) and synthesised compounds (leukotrienes, prostaglandins, cytokines). These mediators induce bronchoconstriction, vascular permeability, mucus secretion and recruitment of inflammatory cells, notably eosinophils and lymphocytes. Beyond acute responses, mast cells contribute to chronic remodelling by promoting goblet cell hyperplasia, smooth muscle proliferation and extracellular matrix deposition. Progenitor recruitment and local differentiation further amplify mast cell density in the airway wall, correlating with disease severity. Recent insights have elucidated the complexity of receptor-mediated activation pathways, the interplay with airway structural cells and the potential for targeting proteases and receptor axes to modulate mast cell function and ameliorate asthmatic pathology.

Research from Nature Portfolio

Seminal work has revealed a pathway in which a member of the tumour necrosis factor superfamily engages its cognate receptor on mast cells to enhance IgE-dependent signalling and mediator release. Experimental models demonstrate that disrupting this receptor–ligand interaction after allergen sensitisation attenuates airway hyperreactivity, reduces inflammatory cell infiltration and limits tissue remodelling. Genetic or pharmacological blockade of the receptor on mast cells diminishes antigen-specific antibody production and airway remodelling, underscoring its role in driving multiple features of asthma pathology.

Mast Cell Dynamics in Asthmatic Inflammation publication trend

The graph below shows the total number of articles in mast cell dynamics in asthmatic inflammation across all publications each year (not limited to Nature Index journals).

Technical terms

Mast cell: Tissue-resident immune cell containing granules of histamine and proteases that mediates allergic and inflammatory responses.

Degranulation: The process by which mast cells release granule contents into surrounding tissue, triggering inflammation.

Tryptase: A serine protease abundant in mast cell granules that promotes bronchoconstriction and tissue remodelling.

Goblet cell hyperplasia: An increase in mucus-producing cells in the airway epithelium associated with chronic inflammation.

Airway remodelling: Structural changes in the bronchial wall, including smooth muscle growth, extracellular matrix deposition and epithelial alterations.

Eosinophil: A type of white blood cell recruited by mast cell mediators that contributes to airway tissue damage and hyperresponsiveness.

References

1. A TNFRSF14-FcɛRI-mast cell pathway contributes to development of multiple features of asthma pathology in mice. Nature Communications (2016).
2. Nafamostat has anti-asthmatic effects associated with suppressed pro-inflammatory gene expression, eosinophil infiltration and airway hyperreactivity. Frontiers in Immunology (2023).
3. Mast Cell Tryptase Promotes Airway Remodeling by Inducing Anti-Apoptotic and Cell Growth Properties in Human Alveolar and Bronchial Epithelial Cells. Cells (2023).
4. Monensin Suppresses Multiple Features of House Dust Mite-Induced Experimental Asthma in Mice. Inflammation (2024).