Inflammasome Activation in Allergic Airway Inflammation

Allergic airway inflammation, as seen in asthma and rhinitis, is driven by orchestrated innate and adaptive immune responses that culminate in airway hyperresponsiveness, mucus overproduction and tissue remodelling. Central to early innate signalling is the assembly of multiprotein inflammasomes, most notably the NLRP3 complex, which acts as a sensor of both exogenous allergens and endogenous danger signals. Upon activation, this platform recruits and activates caspase-1, resulting in the maturation and release of interleukin-1β (IL-1β) and interleukin-18 (IL-18). These cytokines amplify type 2 and type 17 immune pathways, recruit neutrophils and eosinophils, and drive the epithelial–mesenchymal interactions that underpin remodelling. In parallel, inflammasome-dependent pyroptotic cell death, mediated by gasdermin D pore formation, can exacerbate barrier dysfunction and further propagates inflammation. Emerging evidence highlights the contribution of upstream triggers such as TLR4-NF-κB signalling, mitochondrial reactive oxygen species and allergen-induced epithelial stress in lowering the activation threshold of NLRP3. The resulting feed-forward loops between airway epithelium, resident macrophages and recruited leukocytes underpin both acute exacerbations and chronic progression of allergic airway disease. A comprehensive understanding of these pathways has revealed potential intervention points for novel therapies aimed at tempering inflammasome activity without compromising host defence.

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Inflammasome Activation in Allergic Airway Inflammation publication trend

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

Technical terms

NLRP3 inflammasome: A cytosolic multiprotein complex that senses cellular stress or pathogen-associated signals and activates caspase-1.

Caspase-1: An inflammatory protease that cleaves pro-IL-1β and pro-IL-18 into their active forms and initiates pyroptosis.

Pyroptosis: A form of programmed cell death characterised by gasdermin D-mediated pore formation, cell swelling and release of inflammatory contents.

Gasdermin D: The effector protein of pyroptosis; once cleaved by caspase-1, its N-terminal fragment forms membrane pores.

Interleukin-1β (IL-1β): A pro-inflammatory cytokine released upon inflammasome activation that drives leukocyte recruitment and airway hyperresponsiveness.

References

1. Gasdermin D silencing alleviates airway inflammation and remodeling in an ovalbumin-induced asthmatic mouse model. Cell Death & Disease (2024).
2. MiR-146a-5p engineered hucMSC-derived extracellular vesicles attenuate Dermatophagoides farinae-induced allergic airway epithelial cell inflammation. Frontiers in Immunology (2024).
3. MUC1 attenuates neutrophilic airway inflammation in asthma by reducing NLRP3 inflammasome-mediated pyroptosis through the inhibition of the TLR4/MyD88/NF-κB pathway. Respiratory Research (2023).
4. NLRP3 inflammasome activation by mitochondrial ROS in bronchial epithelial cells is required for allergic inflammation. Cell Death & Disease (2014).