Dysregulated metabolism of polyunsaturated fatty acids in eosinophilic allergic diseases

Abstract

Polyunsaturated fatty acids (PUFAs), represented by the omega-6 fatty acid arachidonic acid (AA) and omega-3 fatty acid docosahexaenoic acid (DHA), are essential components of the human body. PUFAs are converted enzymatically into bioactive lipid mediators, including AA-derived cysteinyl leukotrienes (cys-LTs) and lipoxins and DHA-derived protectins, which orchestrate a wide range of immunological responses. For instance, eosinophils possess the biosynthetic capacity of various lipid mediators through multiple enzymes, including 5-lipoxygenase and 15-lipoxygenase, and play central roles in the regulation of allergic diseases. Dysregulated metabolism of PUFAs is reported, especially in severe asthma, aspirin-exacerbated respiratory disease, and eosinophilic chronic rhinosinusitis (ECRS), which is characterized by the overproduction of cys-LTs and impaired synthesis of pro-resolving mediators. Recently, by performing a multi-omics analysis (lipidomics, proteomics, and transcriptomics), we demonstrated the metabolic derangement of eosinophils in inflamed tissues of patients with ECRS. This abnormality occurred subsequent to altered enzyme expression of gamma-glutamyl transferase-5. In this review, we summarize the previous findings of dysregulated PUFA metabolism in allergic diseases, and discuss future prospective therapeutic strategies for correcting this imbalance.

Keywords: 15-lipoxygenase; Aspirin-exacerbated respiratory disease; Cysteinyl leukotrienes; Eosinophilic chronic rhinosinusitis; Eosinophils; Severe asthma.