Eosinophil Extracellular Trap Mechanisms in Allergic Inflammation

Eosinophil extracellular traps (EETs) are filamentous networks of decondensed chromatin studded with eosinophil-derived granule proteins that emerge in response to infectious, allergic and sterile stimuli. Formation of these structures—termed EETosis—relies on histone citrullination, reactive oxygen species generation and membrane permeabilisation, culminating in release of cell-free DNA (cfDNA), major basic protein and other cytotoxic mediators. While EETs contribute to host defence by immobilising pathogens, their persistence in airways, nasal mucosa and skin can provoke tissue damage, mucus plugging and sustained type 2 inflammation. Excessive EET formation is implicated in asthma exacerbations, chronic rhinosinusitis, atopic dermatitis and eosinophilic oesophagitis. Understanding the balance between protective and pathological roles of EETs has stimulated development of targeted interventions—ranging from DNase treatments to PAD4 inhibitors and nanoparticle platforms—to modulate trap formation and mitigate allergic disease severity.

Research from Nature Portfolio

Recent studies have shown that the burden of EETs in chronic rhinosinusitis correlates strongly with clinical measures of disease severity. Quantitative analysis of trap formation in patient tissue revealed that EET density parallels tissue eosinophilia, radiographic opacification scores and olfactory loss, irrespective of polyp status. These findings highlight the prognostic value of EET quantification and support strategies that selectively attenuate trap release to improve surgical and medical management of eosinophilic airway disease.

Eosinophil Extracellular Trap Mechanisms in Allergic Inflammation publication trend

The graph below shows the total number of articles in eosinophil extracellular trap mechanisms in allergic inflammation across all publications each year (not limited to Nature Index journals).

Technical terms

Eosinophil Extracellular Trap (EET): A web of decondensed chromatin fibres decorated with eosinophil granule proteins, released to trap pathogens and modulate inflammation.

EETosis: A specialised form of cell death in which eosinophils release extracellular traps following chromatin decondensation and membrane disruption.

Charcot-Leyden Crystal (CLC): Needle-like crystals composed of galectin-10, formed upon eosinophil activation and implicated in type 2 immune responses.

Citrullination: Post-translational conversion of arginine residues to citrulline by peptidylarginine deiminases, facilitating chromatin relaxation during trap formation.

Protein Arginine Deiminase 4 (PAD4): Enzyme responsible for histone citrullination, a critical step in extracellular trap release.

Cell-free DNA (cfDNA): Extracellular fragments of nuclear or mitochondrial DNA that can activate pattern recognition receptors such as TLR9.

Toll-like Receptor 9 (TLR9): Endosomal receptor that recognises unmethylated CpG DNA motifs, promoting innate immune activation and inflammatory signalling.

References

1. Eosinophil extracellular trap formation is closely associated with disease severity in chronic rhinosinusitis regardless of nasal polyp status. Scientific Reports (2019).
2. Functional 2D Nanoplatforms Alleviate Eosinophilic Chronic Rhinosinusitis by Modulating Eosinophil Extracellular Trap Formation. Advanced Science (2024).
3. Ym1 protein crystals promote type 2 immunity. eLife (2024).
4. Inhibition of EETosis with an anti-citrullinated histone antibody: a novel therapeutic approach for eosinophilic inflammatory disorders. Frontiers in Immunology (2025).