Mast Cell Biology and Pathophysiology

Mast cells are long‐lived, tissue‐resident immune cells derived from the myeloid lineage and strategically positioned at barrier surfaces such as skin, airways and the gastrointestinal tract. Their activation culminates in degranulation and the selective release of a complex array of preformed and de novo synthesised mediators, including histamine, proteases, cytokines and lipid mediators. In homeostasis, mast cells regulate vascular tone, promote wound healing, contribute to host defence against pathogens and participate in venom detoxification. Their phenotype and functional repertoire are moulded by the local microenvironment, leading to marked heterogeneity across tissues. Dysregulated mast cell activation underlies the pathophysiology of allergic disorders, asthma and anaphylaxis, while chronic mast cell–driven inflammation contributes to autoimmunity, fibrosis, neuroinflammatory conditions and tumourigenesis. Emerging evidence highlights bidirectional communication between mast cells and the nervous system, positioning them as key modulators of neuroimmune circuits. Understanding the contextual signals that govern mast cell responses is essential for the development of targeted therapies in diverse disease settings.

Research from Nature Portfolio

Recent studies have revealed that mucosal mast cells armed with antigen-specific IgE and Th2 cytokine priming constitute a critical immunological sensor for ingestion of innocuous antigens. Upon antigen challenge, these cells engage complex signalling networks to transmit avoidance signals to the central nervous system, thereby preventing unnecessary inflammatory responses and tissue damage. In the context of autoimmune joint disease, synovial mast cells exposed to an inflammatory milieu upregulate MHC class II and costimulatory molecules and degranulate via the MRGPRX2 receptor. Dual intervention with IL-17A neutralisation and mast cell stabilisation markedly attenuates arthritis severity and bone erosion in experimental models. Furthermore, in gastric cancer, tumour-derived interleukin-33 activates mast cells through the ST2 receptor, driving macrophage recruitment, neovascularisation and tumour growth. Disruption of the IL-33–mast cell axis diminishes macrophage-associated factors and reduces tumour burden, highlighting a tractable therapeutic pathway.

Mast Cell Biology and Pathophysiology publication trend

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

Technical terms

Degranulation: The process by which mast cells release granule‐stored mediators into the extracellular space upon activation.

Microenvironment: The local cellular and molecular milieu that influences mast cell phenotype and function.

MRGPRX2: A G protein‐coupled receptor on mast cells mediating non‐IgE-dependent activation and degranulation.

IgE: Immunoglobulin E, an antibody isotype that binds to mast cell FcεRI receptors and triggers allergic responses.

Angiogenesis: Formation of new blood vessels driven by mast cell-derived growth factors and proteases.

Barrier function: The capacity of epithelial or endothelial layers to regulate selective permeability and maintain tissue integrity.

References

1. Mast cells link immune sensing to antigen-avoidance behaviour. Nature (2023).
2. Synovial microenvironment-influenced mast cells promote the progression of rheumatoid arthritis. Nature Communications (2024).
3. Mast Cell: A Multi-Functional Master Cell. Frontiers in Immunology (2016).
4. Mast Cell Mediators: Their Differential Release and the Secretory Pathways Involved. Frontiers in Immunology (2014).
5. Role of Mast Cells in Shaping the Tumor Microenvironment. Clinical Reviews in Allergy & Immunology (2019).
6. IL-33-mediated mast cell activation promotes gastric cancer through macrophage mobilization. Nature Communications (2019).
7. Intestinal Mucosal Mast Cells: Key Modulators of Barrier Function and Homeostasis. Cells (2019).