Cysteinyl leukotriene metabolism of human eosinophils in allergic disease

Abstract

Eosinophils are multifaceted immune cells with diverse functions that enhance allergic inflammation. Cysteinyl leukotrienes (cys-LTs), mainly synthesized in eosinophils, are a class of inflammatory lipid mediators produced via multiple enzymatic reactions from arachidonic acid. Multiple clinical studies have reported dysregulated fatty acid metabolism in severe asthma and aspirin-exacerbated respiratory diseases. Therefore, understanding the mechanism responsible for this metabolic abnormality has attracted a lot of attention. In eosinophils, various stimuli (including cytokines, chemokines, and pathogen-derived factors) prime and/or induce leukotriene generation and secretion. Cell-cell interactions with component cells (endothelial cells, epithelial cells, fibroblasts) also enhance this machinery to augment allergic responses. Nasal polyp-derived eosinophils from patients with eosinophilic rhinosinusitis present a characteristic fatty acid metabolism with selectively higher production of leukotriene D₄. Interestingly, type 2 cytokines and microbiome components might be responsible for this metabolic change with altered enzyme expression. Here, we review the regulation of fatty acid metabolism, especially cys-LT metabolism, in human eosinophils toward allergic inflammatory status.