Dendritic Cell Modulation in Allergic Airway Disease

Allergic airway diseases, including asthma and allergic rhinitis, arise from an inappropriate immune response to harmless environmental antigens. Central to this process are dendritic cells (DCs), which capture inhaled allergens in the lung, migrate to draining lymph nodes and direct naïve T cells towards type 2 (Th2) or type 17 (Th17) programmes. Distinct DC subsets—classical type 1 DCs (cDC1s), type 2 DCs (cDC2s), plasmacytoid DCs (pDCs) and monocyte-derived DCs—exert divergent influences on T-cell fate, promoting either allergic inflammation or immune tolerance. Recent advances have revealed key molecular switches, including pattern-recognition receptors, transcription factors and signalling kinases, that modulate DC function under allergic conditions. Understanding these pathways holds promise for novel interventions, such as allergen-specific immunotherapy and targeted modulation of DC subsets, with the potential to restore immune balance and prevent chronic airway hyperresponsiveness and tissue remodelling.

Research from Nature Portfolio

New insights into the orchestration of eosinophil recruitment by lung DC subsets have emerged from work demonstrating that, in the memory phase of chronic allergy, cDC1s rely on nitric oxide derived from CD11b+ cDC2s to induce the chemokines CCL17 and CCL22 and attract eosinophils to the airway wall. At later stages, a separate CD24+ cDC2 population secretes transforming growth factor-β1 to dampen chemokine expression and restrain eosinophil influx, revealing a dynamic two-step mechanism that shapes allergic recall responses.

Another seminal study has identified DNA-dependent protein kinase (DNA-PK) activation as a critical regulator of DC-mediated sensitisation to house dust mite. DNA-PK phosphorylation in DCs enhances antigen processing and presentation, driving a potent Th2 response and airway inflammation. Pharmacological inhibition or genetic ablation of DNA-PK in DCs attenuates allergic sensitisation and ameliorates established airway disease, pointing to DNA-PK as a promising target for therapeutic modulation of allergic airway inflammation.

Dendritic Cell Modulation in Allergic Airway Disease publication trend

The graph below shows the total number of articles in dendritic cell modulation in allergic airway disease across all publications each year (not limited to Nature Index journals).

Technical terms

Dendritic cell (DC): Antigen-presenting immune cell that bridges innate and adaptive immunity in peripheral tissues and lymphoid organs.

cDC1 / cDC2: Distinct subsets of classical DCs specialised in cross-presentation (cDC1) or Th2/Th17 induction (cDC2) in allergic contexts.

DNA-dependent protein kinase (DNA-PK): Serine/threonine kinase involved in DNA repair and, in DCs, in processing and presentation of allergen-derived peptides.

Transcription factor EB (TFEB): Master regulator of lysosomal biogenesis and endocytic pathways that modulates DC antigen-presentation capacity.

C-type lectin receptor (CLR): Carbohydrate-recognition receptor on DCs that binds allergen glycans, driving T-cell polarisation or tolerance.

Tolerogenic DC: Subset of DCs conditioned to induce regulatory T cells and suppress pathological immune responses to allergens.

References

1. Dendritic Cells: Critical Regulators of Allergic Asthma. International Journal of Molecular Sciences (2020).
2. Eosinophil recruitment is dynamically regulated by interplay among lung dendritic cell subsets after allergen challenge. Nature Communications (2018).
3. Dendritic cells induce Th2-mediated airway inflammatory responses to house dust mite via DNA-dependent protein kinase. Nature Communications (2015).
4. TFEB regulates dendritic cell antigen presentation to modulate immune balance in asthma. Respiratory Research (2024).
5. C-Type Lectin Receptor Mediated Modulation of T2 Immune Responses to Allergens. Current Allergy and Asthma Reports (2023).