Metabolism of Epithelial Cells in Health and Allergic Disease: Collegium Internationale Allergologicum Update 2021.

Concomitant dramatic increase in prevalence of allergic and metabolic diseases is part of a modern epidemic afflicting technologically advanced societies. While clinical evidence points to clear associations between various metabolic factors and atopic disease, there is still a very limited understanding of the mechanisms that link the two. Dysregulation of central metabolism in metabolic syndrome, obesity, diabetes, and dyslipidemia has a systemic impact on multiple tissues and organs, including cells of the epithelial barrier. While much of epithelial research in allergy has focused on the immune-driven processes, a growing number of recent studies have begun to elucidate the role of metabolic components of disease. This review will revisit clinical evidence for the relationship between metabolic and allergic diseases, as well as discuss potential mechanisms driving metabolic dysfunction of the epithelial barrier. Among them, novel studies highlight links between dysregulation of the insulin pathway, glucose metabolism, and loss of epithelial differentiation in asthma. Studies of mitochondrial structure and bioenergetics in lean and obese asthmatic phenotypes recently came to light to provide a novel framework linking changes in tricarboxylic acid cycle and oxidative phosphorylation with arginine metabolism and nitric oxide bioavailability. New research established connections between arachidonate metabolism, autophagy, and airway disease, as well as systemic dyslipidemia in atopic dermatitis and ceramide changes in the epidermis. Taken together, studies of metabolism have a great potential to open doors to a new class of therapeutic strategies, better characterization of disease endotypes, as well as enable a systems biology approach to mechanisms of allergic disease.