Innate Immune Responses in Allergic Airway Inflammation

Allergic airway inflammation is initiated when inhaled allergens breach the epithelial barrier and activate airway structural cells to release epithelial-derived cytokines, often termed alarmins, including interleukin-33, interleukin-25 and thymic stromal lymphopoietin. These signals engage pattern recognition receptors on resident dendritic cells and macrophages, driving their maturation and recruitment of circulating monocytes and neutrophils. Concurrently, mast cells and basophils degranulate in response to IgE cross-linking, amplifying local vascular permeability and bronchoconstriction. Critically, group 2 innate lymphoid cells (ILC2) respond rapidly to alarmins by producing type 2 cytokines such as IL-5 and IL-13, thereby orchestrating eosinophil influx, goblet-cell hyperplasia and mucus overproduction. Inflammasome pathways, notably the NLRP3 complex, further modulate cytokine maturation and pyroptosis, accentuating tissue remodelling. Emerging evidence reveals that metabolic programmes within these innate populations dictate activation thresholds and effector output, linking nutrient sensing and lipid metabolism to inflammatory intensity. This multifaceted innate network shapes subsequent adaptive Th2 and B-cell responses, and its dysregulation underpins the pathogenesis of asthma and allergic rhinitis. Understanding the interplay of barrier dysfunction, cellular cross-talk and immunometabolic control offers new avenues for precision therapies aimed at intercepting innate drivers of airway allergy.

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Innate Immune Responses in Allergic Airway Inflammation publication trend

The graph below shows the total number of articles in innate immune responses in allergic airway inflammation across all publications each year (not limited to Nature Index journals).

Technical terms

Alarmin: Epithelial-derived cytokine (e.g. IL-33, TSLP) released on tissue stress to alert innate immune cells.

Innate lymphoid cell (ILC2): Tissue-resident lymphoid cell subset that lacks antigen receptors and secretes type 2 cytokines in response to cytokine signals.

Pattern recognition receptor (PRR): Germline-encoded receptor (e.g. Toll-like receptor, NLRP3) that detects conserved microbial or damage-associated molecular patterns.

Mechanistic target of rapamycin (mTOR): Central kinase integrating nutrient and cytokine signals to regulate cell growth, metabolism and effector functions.

Peroxisome proliferator-activated receptor-gamma (PPAR-γ): Lipid-sensing nuclear receptor that controls transcriptional programmes for lipid metabolism and inflammatory gene expression.

References

1. Metabolic requirements of type 2 lymphocytes in allergic disease. Current Opinion in Immunology (2024).
2. Analysis of lipid uptake, storage, and fatty acid oxidation by group 2 innate lymphoid cells. Frontiers in Immunology (2024).
3. IL-33 induces innate lymphoid cell–mediated airway inflammation by activating mammalian target of rapamycin. Journal of Allergy and Clinical Immunology (2012).