Allergic Inflammation and Immune Response Modulation

Allergic inflammation arises from a maladaptive immune response to harmless environmental proteins, or allergens, leading to a cascade of cellular and molecular events that culminate in tissue damage, clinical symptoms and chronic disease in predisposed individuals. Initiation begins with allergen sampling at epithelial surfaces by specialised cells and the release of alarmins such as interleukin-33, thymic stromal lymphopoietin and interleukin-25 from barrier epithelial cells. These molecules skew local dendritic cells towards a type 2 profile, promoting T helper 2 (Th2) cell differentiation and the production of cytokines (IL-4, IL-5, IL-13) that drive IgE isotype switching in B cells, eosinophil recruitment and mast cell sensitisation. Upon re-exposure, allergen-specific IgE bound to effector cells triggers degranulation and the release of histamine, leukotrienes and prostaglandins, producing acute symptoms and perpetuating chronic inflammation. Emerging evidence reveals that non-protein components of the allergenic source, including lipids and proteases, and environmental co-factors such as microbial products, can amplify or modulate this response by interacting with pattern recognition receptors on epithelial and immune cells. Immune response modulation explores therapeutic avenues to restore tolerance or redirect inflammation, encompassing biologicals that target IgE, Th2 cytokines, cell surface receptors and signal transduction pathways, as well as allergen-specific immunotherapy. The global burden of allergic diseases underscores the need for a detailed understanding of these interconnected pathways to inform precision interventions and reduce morbidity worldwide.

Research from Nature Portfolio

Recent studies have demonstrated that pollen proteases can selectively degrade epithelial cell junctions, facilitating allergen access and influencing viral entry. Investigations using ex vivo respiratory mucosal explants and primary epithelial cultures reveal that serine proteases from grass and tree pollens irreversibly disrupt columnar cell anchorage while sparing basal cells, thereby compromising barrier integrity. This epithelial damage not only potentiates Th2-skewed immune responses but also enhances susceptibility to alphaherpesvirus infection by creating permissive entry points. These findings highlight dual pathways through which allergen-derived proteases contribute to both allergic sensitisation and increased risk of respiratory viral disease.

Allergic Inflammation and Immune Response Modulation publication trend

The graph below shows the total number of articles in allergic inflammation and immune response modulation across all publications each year (not limited to Nature Index journals).

Technical terms

Th2 cells: A subset of T helper lymphocytes that produce type 2 cytokines (IL-4, IL-5, IL-13), driving eosinophilic inflammation and IgE production.

Immunoglobulin E (IgE): Antibody isotype central to allergic responses, binding allergens and triggering mast cell and basophil degranulation.

Dendritic cells: Antigen-presenting cells that sample allergens and orchestrate T cell polarisation towards Th1, Th2 or regulatory fates.

Epithelial barrier: Structural and functional lining of mucosal surfaces that prevents allergen penetration and maintains immune homeostasis.

Pattern recognition receptors (PRRs): Innate immune sensors (e.g. Toll-like receptors) that detect pathogen-associated or allergen-associated molecular patterns.

Alarmins: Endogenous signalling proteins (e.g. IL-33, TSLP) released upon epithelial damage to activate innate and adaptive immunity.

Proteases: Enzymes that cleave proteins, in this context allergen-derived proteases that disrupt epithelial junctions and modulate immune responses.

References

1. Allergen Recognition by Innate Immune Cells: Critical Role of Dendritic and Epithelial Cells. Frontiers in Immunology (2013).
2. Initiating pollen sensitization – complex source, complex mechanisms. Clinical and Translational Allergy (2020).
3. Pollens destroy respiratory epithelial cell anchors and drive alphaherpesvirus infection. Scientific Reports (2019).
4. Modulation of Distinct Asthmatic Phenotypes in Mice by Dose-Dependent Inhalation of Microbial Products. Environmental Health Perspectives (2013).
5. Chinese Birch Pollen Allergy and Immunotherapy in Mice. Inflammation (2019).