Mechanisms and Treatments for Allergic Rhinitis

Allergic rhinitis is characterised by an IgE-mediated hypersensitivity to airborne allergens, leading to nasal itching, sneezing, rhinorrhoea and congestion. Allergen exposure triggers cross-linking of IgE on mast cells, prompting degranulation and the release of histamine, leukotrienes and cytokines. A skew towards T helper 2 (Th2) responses drives the production of interleukins 4, 5 and 13, promoting eosinophil recruitment, mucus hypersecretion and tissue remodelling. Emerging evidence highlights roles for innate immune cells—such as CD169+ macrophages and dendritic cells—in modulating oxidative stress via Nrf2/HO-1 signalling and shaping T-cell differentiation. Oxidative processes further amplify mucosal inflammation. Current treatment includes oral or intranasal antihistamines, intranasal corticosteroids and allergen immunotherapy, which aim to restore immune tolerance. Innovative approaches under investigation target specific molecular pathways: monoclonal antibodies against IgE or key cytokines, gene silencing of ion channels to limit cell activation, sustained-release formulations of corticosteroids for prolonged efficacy, and small molecules that rebalance Th1/Th2/Th17 and regulatory T-cell networks while boosting antioxidant defences. Integration of these strategies promises more precise control of symptoms and disease modification.

Research from Nature Portfolio

Gene silencing of the calcium-activated potassium channel KCa3.1 via short hairpin RNA in a murine model markedly reduced ovalbumin-specific IgE, histamine release and Th2 cytokines. This intervention attenuated mast cell activation and goblet cell hyperplasia by inhibiting PI3K/AKT signalling, suggesting KCa3.1 as a novel target to suppress allergic inflammation. α-Lipoic acid administration in sensitised mice rebalanced Th17 and regulatory T-cell populations, increased IL-10 and Foxp3 expression, and suppressed pro-inflammatory cytokines. Concurrent activation of the Nrf2/HO-1 antioxidant pathway and inhibition of NF-κB/IκB reduced oxidative stress and tissue inflammation in nasal and lung mucosa, highlighting the potential of redox-modulating therapies.

Mechanisms and Treatments for Allergic Rhinitis publication trend

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

Technical terms

IgE: Immunoglobulin E, an antibody class central to allergic responses.

Th2 cells: T helper lymphocytes that produce IL-4, IL-5 and IL-13, driving eosinophilic inflammation.

Cytokines: Small proteins secreted by immune cells to coordinate inflammation and tolerance.

Dendritic cells (DCs): Antigen-presenting cells that direct T-cell differentiation.

Pyroptosis: Inflammatory programmed cell death mediated by gasdermin proteins.

KCa3.1: Calcium-activated potassium channel involved in cell activation and mediator release.

shRNA: Short hairpin RNA used to silence specific gene expression.

Nrf2/HO-1 pathway: Antioxidant signalling cascade that mitigates oxidative stress.

Sustained-release formulation: Drug delivery system designed for prolonged therapeutic effect.

References

1. CD169+ Macrophages Mediate the Immune Response of Allergic Rhinitis Through the Keap1/Nrf2/HO‐1 Axis. Advanced Science (2024).
2. Long-acting anti-inflammatory injectable DEX-Gel with sustained release and self-healing properties regulates TH1/TH2 immune balance for minimally invasive treatment of allergic rhinitis. Journal of Nanobiotechnology (2024).
3. Allergen-induced CD11c + dendritic cell pyroptosis aggravates allergic rhinitis. Cell Communication and Signaling (2023).
4. Lentiviral shRNA against KCa3.1 inhibits allergic response in allergic rhinitis and suppresses mast cell activity via PI3K/AKT signaling pathway. Scientific Reports (2015).
5. Anti-allergic rhinitis activity of α-lipoic acid via balancing Th17/Treg expression and enhancing Nrf2/HO-1 pathway signaling. Scientific Reports (2020).