Eosinophil Biology and Inflammation Modulation

Eosinophils are specialised white blood cells that play crucial roles in host defence, tissue homeostasis and the regulation of inflammation. They are distinguished by their bilobed nuclei and cytoplasmic granules containing a range of bioactive proteins, including major basic protein and eosinophil cationic protein, which can be deployed against parasites but also contribute to tissue injury in allergic and chronic inflammatory diseases. Eosinophil development is driven by interleukin-5 and other cytokines within the bone marrow, followed by mobilisation into the circulation and recruitment to peripheral tissues in response to chemokines and lipid mediators. Once at sites of inflammation, eosinophils engage in degranulation, release of reactive oxygen species and production of cytokines, thereby orchestrating local immune responses. In recent years, attention has focused on the mechanisms that regulate eosinophil survival and death, notably the signalling pathways that modulate apoptosis and necrosis under varying microenvironmental conditions. Advances in our understanding of eosinophil regulation have yielded new therapeutic strategies aimed at limiting their persistence in tissues, including monoclonal antibodies directed against interleukin-5, small molecules targeting eosinophil activation pathways and pH-sensitive modulators of cell viability. By modulating eosinophil lifespan and effector function, these approaches hold promise for the treatment of asthma, eosinophilic oesophagitis and other disorders characterised by eosinophil-driven inflammation.

Research from Nature Portfolio

Recent studies have demonstrated that modulation of neuropeptide signalling can substantially attenuate eosinophil-driven airway inflammation. In a murine model of allergen-induced asthma, inhaled administration of a metabolic hormone analogue markedly reduced airway hyperresponsiveness, peribronchiolar eosinophil accumulation and subepithelial fibrosis. This therapy acted through elevation of intracellular cyclic AMP within both eosinophils and T lymphocytes, leading to diminished production of type 2 cytokines and chemokines. The anti-inflammatory effect was reversible by cyclooxygenase inhibition, indicating interplay between prostanoid pathways and cyclic AMP signalling. These findings establish a novel axis for controlling eosinophil recruitment and function in the lung, and illustrate the potential of repurposed endocrine mediators in the treatment of steroid-resistant airway disease.

Eosinophil Biology and Inflammation Modulation publication trend

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

Technical terms

Eosinophil: A granulocytic leukocyte containing cytoplasmic granules with cytotoxic proteins, involved in parasitic defence and allergic inflammation.

Degranulation: The process by which eosinophils release their granule contents into the extracellular space.

Apoptosis: Programmed cell death characterised by cell shrinkage, DNA fragmentation and phagocytic removal without eliciting inflammation.

Cyclic AMP (cAMP): A second messenger that mediates intracellular signalling, often promoting anti-inflammatory effects in immune cells.

G protein-coupled receptor 65 (GPR65): A proton-sensing receptor expressed on eosinophils that links extracellular acidity to intracellular signalling pathways.

Chemokine: A class of small cytokines that direct the migration of immune cells towards sites of inflammation or injury.

References

1. Effects of Lidocaine-Derived Organic Compounds on Eosinophil Activation and Survival. Molecules (2023).
2. Eosinophil viability is increased by acidic pH in a cAMP- and GPR65-dependent manner. Blood (2009).
3. Gold Nanoparticles Inhibit Steroid-Insensitive Asthma in Mice Preserving Histone Deacetylase 2 and NRF2 Pathways. Antioxidants (2022).
4. Glucagon reduces airway hyperreactivity, inflammation, and remodeling induced by ovalbumin. Scientific Reports (2019).