Laboratory of Allergic Diseases, NIAID, NIH, 9000 Rockville Pike, NIH Building 10 Room 11N240A, United States.
Laboratory of Allergic Diseases, NIAID, NIH, 9000 Rockville Pike, NIH Building 10 Room 11N240A, United States.
Curr Opin Immunol. 2019 Oct;60:148-155. doi: 10.1016/j.coi.2019.06.002. Epub 2019 Jul 11.
Environmental factors modify disease presentation and severity in allergic disorders. Primary atopic disorders (PADs) are a heterogenous group of single gene disorders that lead to significant atopic and allergic disease manifestations. However, a number of these monogenic diseases have variable penetrance suggesting that gene-gene and/or gene-environment interactions could modulate the clinical phenotype. Environmental factors such as diet, the microbiome at the epithelial-environment interface, the presence and/or extent of infection, and psychologic stress can alter disease phenotypic expression of allergic diseases, and PADs provide discrete contexts in which to understand these influences. We outline how gene-environment interactions likely contribute to a variable penetrance and expressivity in PADs. Dietary modifications of both macronutrients and/or micronutrients alter T-cell metabolism and may influence effector T-cell function. The mucosal microbiome may affect local inflammation and may remotely influence regulatory elements, while psychologic stress can affect mast cell and other allergic effector cell function. Understanding gene-environment interactions in PADs can hopefully provide a foundation for interrogating gene-environment interactions to common allergic disorders, and also present opportunities for personalized interventions based on the altered pathways and environmental influences in affected individuals.
环境因素可改变过敏症的表现和严重程度。原发性特应性疾病（PADs）是一组由单基因疾病组成的异质性疾病，可导致明显的特应性和过敏性疾病表现。然而，这些单基因疾病中有许多具有可变的外显率，这表明基因-基因和/或基因-环境相互作用可能调节临床表型。环境因素，如饮食、上皮-环境界面的微生物组、感染的存在和/或程度以及心理压力，可以改变过敏疾病的疾病表型表达，而 PADs 则提供了理解这些影响的离散背景。我们概述了基因-环境相互作用如何可能导致 PADs 中的可变外显率和表现度。宏量营养素和/或微量营养素的饮食改变可改变 T 细胞代谢，并可能影响效应 T 细胞功能。粘膜微生物组可能会影响局部炎症，并可能远程影响调节元件，而心理压力会影响肥大细胞和其他过敏效应细胞的功能。了解 PADs 中的基因-环境相互作用有望为研究常见过敏疾病中的基因-环境相互作用提供基础，并为受影响个体中改变的途径和环境影响提供基于个性化干预的机会。
