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The following is a summary of “Multiomics analysis identified IL-4–induced IL1RL1high eosinophils characterized by prominent cysteinyl leukotriene metabolism,” published in the July 2024 issue of Allergy and Clinical Immunology by Sunata et al.
Clinical studies indicate that interleukin-4 (IL-4), a type 2 cytokine, is crucial in the development of chronic rhinosinusitis and eosinophilic asthma, yet its direct effects on eosinophils are not well understood.
Researchers conducted a prospective study to elucidate the inflammatory effects of IL-4 on the functions of human eosinophils.
They performed a multiomics analysis, including transcriptomics, proteomics, lipidomics, quantitative RT-PCR, and flow cytometry, using blood eosinophils from healthy subjects stimulated with IL-4, interleukin-5 (IL-5), or a combination of both.
The result indicated that both IL-4 and IL-5 enhance the expression of γ-glutamyl transferase 5, an enzyme responsible for converting leukotriene C4 to leukotriene D4, as shown by transcriptomic and proteomic analyses. IL-4 also selectively increases levels of IL-1 receptor-like 1 (IL1RL1), a receptor for IL-33 and transglutaminase-2. Additional transcriptomic assessments of IL-13-stimulated cells identified similar gene expression changes, with increases in γ-glutamyl transferase 5, transglutaminase-2, and IL1RL1, akin to IL-4 effects. Lipidomic studies revealed that IL-4 and IL-5 together elevated the extracellular release of leukotriene D4. In vitro studies confirmed that STAT6 and IL-4 receptor-α regulate the expression of these proteins when IL-4 and IL-13 are present. Eosinophils from patients with allergic disorder demonstrated the roles of IL-4 and IL-13 in inflamed areas.
Investigators concluded that IL-4 promotes a proallergic phenotype in IL1RL1high eosinophils, driven by cysteinyl leukotriene metabolism via STAT6, highlighting potential therapeutic targets for chronic rhinosinusitis and eosinophilic asthma.
Source: sciencedirect.com/science/article/pii/S0091674924007413
