IL-17 Mediated Inflammation in Allergic Airway Disease

Allergic airway diseases, including asthma and asthma–COPD overlap, involve complex immune interactions in which interleukin-17A (IL-17A) has emerged as a central driver of neutrophilic inflammation and tissue remodelling. Produced predominantly by T helper 17 (Th17) cells, IL-17A acts on epithelial cells, fibroblasts and stromal populations to induce chemokines such as CXCL8 and cytokines including IL-6 and granulocyte-colony stimulating factor. This promotes recruitment and activation of neutrophils, amplifying airway hyperresponsiveness and mucus hypersecretion. A Th2–Th17 crosstalk may shift an initially eosinophilic endotype towards mixed or neutrophilic phenotypes, which are linked to more severe, steroid-resistant disease. Downstream pathways such as NF-κB and Rho kinase contribute to extracellular matrix deposition, smooth muscle hypertrophy and oxidative stress. Worldwide, over 300 million individuals suffer from asthma, and IL-17-driven mechanisms are increasingly recognised as targets for precision therapies aimed at reducing exacerbations, reversing remodelling and restoring lung function.

Research from Nature Portfolio

Recent studies have uncovered an epigenetic mechanism by which airway epithelial SIRT6 governs IL-17A pathogenicity. In murine models of severe asthma, epithelial deletion of Sirt6 markedly attenuated allergen-induced neutrophilic inflammation, chemokine expression and subepithelial fibrosis by reducing RORγt recruitment to the IL-17A promoter. Pharmacological inhibition of SIRT6 similarly diminished airway remodelling and improved lung function, identifying SIRT6 as a potential therapeutic target to modulate IL-17A-driven disease severity.

IL-17 Mediated Inflammation in Allergic Airway Disease publication trend

The graph below shows the total number of articles in il-17 mediated inflammation in allergic airway disease across all publications each year (not limited to Nature Index journals).

Technical terms

Interleukin-17A (IL-17A): a proinflammatory cytokine produced by Th17 cells that promotes neutrophil recruitment and activation.

T helper 17 (Th17) cell: a subset of CD4+ T lymphocytes characterised by production of IL-17A, central to neutrophilic inflammation.

RORγt: transcription factor that controls Th17 differentiation and IL-17A gene expression.

Chemokine: small signalling protein that directs migration of immune cells towards sites of inflammation.

Airway remodelling: structural changes in airway walls, including fibrosis and smooth muscle hypertrophy, that contribute to chronic airflow obstruction.

Sirtuin 6 (SIRT6): a histone deacetylase that epigenetically regulates gene transcription including IL-17A in airway epithelial cells.

References

1. Epithelial SIRT6 governs IL-17A pathogenicity and drives allergic airway inflammation and remodeling. Nature Communications (2023).
2. Modulating asthma–COPD overlap responses with IL-17 inhibition. Frontiers in Immunology (2023).
3. Interaction of Interleukin-17A with a Th2 Response in a Mouse Model of Allergic Airway Inflammation. Cells (2023).