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.
Int Arch Allergy Immunol

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健康和过敏性疾病中上皮细胞的代谢：国际过敏学会 2021 年更新

过敏性疾病和代谢性疾病患病率的急剧增加是困扰技术先进社会的现代流行病的一部分。虽然临床证据表明各种代谢因素与特应性疾病之间存在明确的关联，但对两者之间联系机制的了解仍然非常有限。代谢综合征、肥胖、糖尿病和血脂异常中的中枢代谢失调对多个组织和器官（包括上皮屏障细胞）产生系统性影响。虽然过敏方面的许多上皮研究都集中在免疫驱动的过程上，但最近越来越多的研究已经开始阐明疾病代谢成分的作用。本综述将重新审视代谢性疾病与过敏性疾病之间关系的临床证据，并讨论驱动上皮屏障代谢功能障碍的潜在机制。其中，新的研究强调了哮喘中胰岛素途径失调、葡萄糖代谢和上皮分化丧失之间的联系。最近对瘦和肥胖哮喘表型的线粒体结构和生物能学的研究揭示了一个新的框架，将三羧酸循环和氧化磷酸化的变化与精氨酸代谢和一氧化氮生物利用度联系起来。新研究建立了花生四烯酸代谢、自噬和气道疾病以及特应性皮炎中的系统性血脂异常和表皮神经酰胺变化之间的联系。总而言之，代谢研究具有巨大的潜力，可以为新型治疗策略、更好地表征疾病内型以及采用系统生物学方法研究过敏性疾病机制打开大门。
Int Arch 过敏免疫