Immunological Mechanisms in Asthma and Allergic Responses

Asthma and allergic responses arise from dysregulated immune interactions at the airway mucosal surface. Barrier disruption by aeroallergens or pollutants triggers epithelial release of alarmins (IL-33, IL-25, TSLP), which activate innate immune cells including dendritic cells and group 2 innate lymphoid cells (ILC2). Dendritic cells present allergenic peptides to naïve CD4+ T cells, driving Th2 polarisation under the influence of IL-4, IL-5 and IL-13. Th2 lymphocytes and ILC2 cooperate to recruit eosinophils and promote B-cell class switching to IgE production. Allergen-specific IgE binds mast cells and basophils, facilitating immediate hypersensitivity on re-exposure. Chronic type-2 inflammation leads to airway hyperresponsiveness, mucus hypersecretion and remodelling. Heterogeneity in asthma endotypes—T2-high versus T2-low—reflects differences in cytokine profiles, cellular infiltrates and response to targeted biologics. Emerging evidence highlights plasticity among T cells, including CD8+ Tc2 subsets, and the role of antiviral responses in exacerbations. Regulatory circuits involving T regulatory cells and epithelial repair mechanisms modulate disease severity. Understanding these interconnected pathways underpins the development of biomarker-guided therapies and global strategies to reduce allergic disease burden.

Research from Nature Portfolio

Recent studies have identified a pivotal role for CD8+ T cells as producers of type-2 cytokines in severe asthma. Emerging from IFNγ+ precursors, these Tc2 cells accumulate during exacerbations and exhibit steroid insensitivity. Experimental models reveal that IL-33 is essential for programming lung Tc cells to secrete IL-4, IL-5 and IL-13, amplifying airway inflammation. These findings broaden the canonical view of Th2-driven disease and suggest novel cellular targets for therapeutic intervention.

Immunological Mechanisms in Asthma and Allergic Responses publication trend

The graph below shows the total number of articles in immunological mechanisms in asthma and allergic responses across all publications each year (not limited to Nature Index journals).

Technical terms

Alarmin: Epithelial-derived cytokine that alerts the immune system to tissue damage or allergen exposure.

Type-2 cytokines: A group of interleukins (IL-4, IL-5, IL-13) that mediate allergic inflammation.

ILC2: Innate lymphoid cells that produce type-2 cytokines independent of antigen specificity.

Th2 cells: CD4+ T helper cells that orchestrate type-2 immune responses.

IgE: Antibody isotype central to allergic sensitisation and immediate hypersensitivity.

Eosinophils: Granulocytes recruited by type-2 cytokines that contribute to airway inflammation.

References

1. Type-2 CD8+ T-cell formation relies on interleukin-33 and is linked to asthma exacerbations. Nature Communications (2023).
2. Longitudinal analysis of the impact of smoking exposure on atopic indices and allergies in early childhood. World Allergy Organization Journal (2023).
3. Is IgE or eosinophils the key player in allergic asthma pathogenesis? Are we asking the right question?. Respiratory Research (2018).
4. Asthma biomarkers in the age of biologics. Allergy, Asthma & Clinical Immunology (2017).
5. Total and specific immunoglobulin E in induced sputum in allergic and non-allergic asthma. PLOS ONE (2020).