Allergy

Allergy encompasses a maladaptive immune response to otherwise harmless environmental proteins or chemicals, marked by the production of allergen-specific IgE antibodies and activation of type 2 immune pathways. On first exposure, dendritic cells process and present allergen peptides to naïve CD4+ T cells, which differentiate into Th2 effectors under the influence of epithelial-derived alarmins (TSLP, IL-25, IL-33). Th2 cytokines (IL-4, IL-5, IL-13) drive B-cell isotype switching to IgE, eosinophil recruitment and mast-cell sensitisation. Re-exposure to allergen cross-links IgE on mast cells and basophils, triggering degranulation and release of histamine, leukotrienes and other mediators that produce immediate symptoms (rhinitis, urticaria, bronchoconstriction). A subsequent late-phase reaction recruits eosinophils and Th2 cells, leading to sustained inflammation and tissue remodelling. Genetic variants affecting barrier integrity (e.g. filaggrin), cytokine signalling (IL-4Rα, IL-13) and innate recognition (TLRs, CD14) influence individual susceptibility, while environmental factors such as pollution, microbial exposure and diet modulate disease expression. Advances in understanding these pathways have underpinned therapies ranging from allergen avoidance and pharmacological inhibition of mediators to precision biologics and immunomodulatory strategies.

Research from Nature Portfolio

New studies reveal that maternal IgG repertoires, shaped by atopic sensitisation to house-dust-mite allergen, can directly modulate human neonatal thymic B cells and innate lymphoid cell subsets. Allergen-specific IgG was shown to alter homing-receptor expression and suppress pro-inflammatory cytokine production, while enhancing IL-10–producing regulatory B10 cells, suggesting a mechanism by which maternal antibodies imprint offspring immune tolerance or predisposition to allergy.

An independent investigation has identified airway epithelial sirtuin 6 (SIRT6) as an epigenetic regulator governing IL-17A pathogenicity in severe asthma. Epithelial deletion or pharmacological inhibition of SIRT6 reduced RORγt recruitment to the IL-17A promoter, attenuated neutrophilic inflammation and fibrosis, and improved lung function, highlighting SIRT6 as a potential target to temper IL-17–driven allergic airway remodelling.

Research from all publishers

In a murine model of allergic asthma, silencing the pyroptosis effector gasdermin D (GSDMD) markedly attenuated IL-1β and IL-18 release, reduced Th17 responses and goblet-cell hyperplasia, and limited both inflammatory infiltration and tissue remodelling. These findings underscore GSDMD as a novel target to disrupt inflammasome-dependent airway injury in asthma.

Efforts to improve community management of anaphylaxis have led to development of a needle-free epinephrine nasal spray that incorporates an absorption enhancer. Early clinical and animal studies demonstrate that this intranasal formulation achieves pharmacokinetic and pharmacodynamic profiles comparable to intramuscular injection, offering a promising alternative for rapid adrenaline delivery in emergency allergic reactions.

Allergy publication trend

The graph below shows the total number of articles in allergy across all publications each year (not limited to Nature Index journals).

Technical terms

FcγRIIB: An inhibitory IgG Fc receptor on B cells that attenuates B-cell receptor signalling and modulates antibody responses.

B10 cells: A subset of regulatory B cells defined by IL-10 production, contributing to immune tolerance.

Sirtuin 6 (SIRT6): A nuclear deacetylase that epigenetically regulates transcription factors such as RORγt to control cytokine gene expression.

Gasdermin D (GSDMD): The pore-forming effector protein of pyroptosis; cleaved by caspase-1 to initiate inflammatory cell death.

Pyroptosis: A lytic, pro-inflammatory form of programmed cell death mediated by inflammasome activation and gasdermin-pore formation.

Anaphylaxis: A rapid, systemic type I hypersensitivity reaction characterised by mast-cell degranulation, vasodilation, bronchospasm and hypotension requiring urgent epinephrine.

References

1. Overview and Understanding of Allergic Reactions and Allergic Disease.
2. Non-atopic Neonatal Thymic Innate Lymphoid Cell Subsets (ILC1, ILC2, and ILC3) Identification and the Modulatory Effect of IgG From Dermatophagoides Pteronyssinus (Derp)-Atopic Individuals. Frontiers in Allergy (2021).
3. IgG from Dermatophagoides pteronyssinus (Der p)-atopic individuals modulates non-atopic thymic B cell phenotype (alfa-4/beta-7) and cytokine production (IFN-γ, IL-9, and IL-10) with direct membrane interaction. Scientific Reports (2024).
4. Epithelial SIRT6 governs IL-17A pathogenicity and drives allergic airway inflammation and remodeling. Nature Communications (2023).
5. Gasdermin D silencing alleviates airway inflammation and remodeling in an ovalbumin-induced asthmatic mouse model. Cell Death & Disease (2024).
6. Development of neffy, an Epinephrine Nasal Spray, for Severe Allergic Reactions. Pharmaceutics (2024).