Photo Credit: Nemes Laszlo
The following is a summary of “An epithelial gene signature of trans-IL-6 signaling defines a subgroup of type 2-low asthma,” published in the December 2024 issue of Pulmonology by El-Husseini et al.
Asthma presents heterogeneous inflammatory phenotypes, categorized as type 2-high and type 2-low, posing challenges in targeted therapy development, particularly for type 2-low inflammation. IL-6 signaling has been implicated in severe asthma, with the cooperation of soluble-IL-6Rα (sIL-6Rα) activating signaling pathways in airway epithelium.
The objective was to investigate the role of sIL-6Rα-amplified IL-6 signaling in airway epithelium and to develop a gene signature indicative of IL-6+sIL-6Rα activity, potentially guiding anti-IL-6 therapy selection in asthma patients. Human airway epithelial cells were stimulated with IL-6, sIL-6Rα, and inhibitors to assess pathway activation, epithelial barrier integrity, and gene expression. The combination of IL-6+sIL-6Rα amplified pathway activation and gene induction in airway epithelial cells compared to IL-6 alone, countered by Olamkicept and Tocilizumab inhibition.
Researchers constructed an IL-6+sIL-6Rα gene signature enriched in bronchial biopsies from asthma patients compared to healthy controls, indicative of heightened local airway IL-6+sIL-6Rα signaling. Moreover, the IL-6+sIL-6Rα gene signature score correlated with lower sputum eosinophil levels in asthma, suggesting its potential as a biomarker for type 2-low asthma. The findings illuminate the role of sIL-6Rα in amplifying IL-6 signaling in bronchial epithelial cells and highlight the association of heightened local airway IL-6+sIL-6Rα signaling with a distinct asthma phenotype characterized by low sputum eosinophils.
Source: respiratory-research.biomedcentral.com/articles/10.1186/s12931-023-02617-w