Molecular Immune Mechanisms in Allergic Airway Diseases

Allergic airway diseases including allergic asthma and rhinitis arise from complex interactions between structural cells of the airway and components of the innate and adaptive immune system. Epithelial barrier dysfunction permits penetration of allergens and inhaled pathogens, leading to release of epithelial alarmins such as TSLP, IL-33 and IL-25. These alarmins activate dendritic cells and innate lymphoid cells type 2 (ILC2s), driving a type 2 immune cascade characterised by Th2 lymphocytes, type 2 cytokines (IL-4, IL-5, IL-13) and immunoglobulin E production. IgE-sensitised mast cells and basophils degranulate upon allergen re-exposure, releasing histamine and proteases that amplify local inflammation. Eosinophils recruited via eotaxins release toxic granule proteins and further cytokines, contributing to airway hyperresponsiveness and mucus hypersecretion. Chronic type 2 inflammation promotes airway remodelling, with goblet cell metaplasia, smooth muscle hypertrophy and subepithelial fibrosis. Emerging evidence emphasises the role of epigenetic regulators such as histone deacetylases and transcriptional modulators in orchestrating chemokine networks that underpin remodelling. Molecular chaperones including heat shock proteins can act both as danger signals and immunomodulators, linking epithelial stress to allergic inflammation. Understanding these mechanisms at a molecular level offers the potential to develop targeted therapies that intervene at critical checkpoints of the allergic cascade.

Research from Nature Portfolio

A novel ultrastructural imaging technique has been developed to coat paraffin-embedded bronchial tissue with an osmium thin film, enhancing scanning electron microscopy contrast and revealing detailed features of mucous cell metaplasia and interstitial fibrosis in an asthma mouse model. Comparison of wild-type and Amphiregulin-deficient mice showed that Amphiregulin is essential for goblet cell changes but not for fibrotic matrix deposition, providing spatial insight into epithelial and stromal remodelling pathways. Concurrent research in paediatric allergic rhinitis has demonstrated upregulation of inducible HSP70 members in nasal mucosal cells, correlating with fractional exhaled nitric oxide levels and clinical symptoms. These findings propose HSP70 expression as a predictive biomarker for lower airway inflammation and asthma risk in symptomatic children, linking nasal and bronchial immune events.

Molecular Immune Mechanisms in Allergic Airway Diseases publication trend

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

Technical terms

Alarmin: Epithelial-derived cytokine released upon barrier damage that initiates type 2 immune responses.

Type 2 immunity: Immune programme characterised by Th2 cells, type 2 cytokines (IL-4, IL-5, IL-13) and eosinophilia.

Innate lymphoid cell 2 (ILC2): Innate immune cell producing type 2 cytokines in response to epithelial alarmins.

Epigenetic deacetylation: Removal of acetyl groups from histone proteins by enzymes such as HDACs to regulate gene expression.

Airway remodelling: Structural changes in the bronchial wall, including goblet cell metaplasia, smooth muscle hypertrophy and subepithelial fibrosis.

Heat shock protein 70 (HSP70): Molecular chaperone upregulated by cellular stress, implicated in protein folding and immune modulation.

References

1. HDAC4 induces the development of asthma by increasing Slug-upregulated CXCL12 expression through KLF5 deacetylation. Journal of Translational Medicine (2021).
2. Inflammatory mediators in nasal secretions of patients with nasal polyposis with and without aspirin sensitivity. Immunity Inflammation and Disease (2023).
3. The new preparation method for paraffin-embedded samples applying scanning electron microscopy revealed characteristic features in asthma-induced mice. Scientific Reports (2022).
4. Diagnostic and Prognostic Risk Assessment of Heat Shock Protein HSPA1B rs2763979 Gene Variant in Asthma. Genes (2022).
5. HSP70 upregulation in nasal mucosa of symptomatic children with allergic rhinitis and potential risk of asthma development. Scientific Reports (2022).