León Beatriz
Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, United States.
Front Allergy. 2023 Jan 10;3:1080153. doi: 10.3389/falgy.2022.1080153. eCollection 2022.
Allergic diseases, including atopic dermatitis, allergic rhinitis, asthma, and food allergy, are caused by abnormal responses to relatively harmless foreign proteins called allergens found in pollen, fungal spores, house dust mites (HDM), animal dander, or certain foods. In particular, the activation of allergen-specific helper T cells towards a type 2 (Th2) phenotype during the first encounters with the allergen, also known as the sensitization phase, is the leading cause of the subsequent development of allergic disease. Infants and children are especially prone to developing Th2 cell responses after initial contact with allergens. But in addition, the rates of allergic sensitization and the development of allergic diseases among children are increasing in the industrialized world and have been associated with living in urban settings. Particularly for respiratory allergies, greater susceptibility to developing allergic Th2 cell responses has been shown in children living in urban environments containing low levels of microbial contaminants, principally bacterial endotoxins [lipopolysaccharide (LPS)], in the causative aeroallergens. This review highlights the current understanding of the factors that balance Th2 cell immunity to environmental allergens, with a particular focus on the determinants that program conventional dendritic cells (cDCs) toward or away from a Th2 stimulatory function. In this context, it discusses transcription factor-guided functional specialization of type-2 cDCs (cDC2s) and how the integration of signals derived from the environment drives this process. In addition, it analyzes observational and mechanistic studies supporting an essential role for innate sensing of microbial-derived products contained in aeroallergens in modulating allergic Th2 cell immune responses. Finally, this review examines whether hyporesponsiveness to microbial stimulation, particularly to LPS, is a risk factor for the induction of Th2 cell responses and allergic sensitization during infancy and early childhood and the potential factors that may affect early-age response to LPS and other environmental microbial components.
过敏性疾病，包括特应性皮炎、过敏性鼻炎、哮喘和食物过敏，是由对相对无害的外来蛋白质（称为变应原）的异常反应引起的，这些变应原存在于花粉、真菌孢子、屋尘螨（HDM）、动物皮屑或某些食物中。特别是，在首次接触变应原（也称为致敏阶段）期间，变应原特异性辅助性T细胞向2型（Th2）表型的激活，是随后过敏性疾病发展的主要原因。婴儿和儿童在初次接触变应原后尤其容易产生Th2细胞反应。此外，在工业化国家，儿童中过敏性致敏和过敏性疾病的发病率正在上升，并且与生活在城市环境中有关。特别是对于呼吸道过敏，在生活于含有低水平微生物污染物（主要是细菌内毒素[脂多糖（LPS）]）的空气传播变应原环境中的儿童中，已显示出对发展过敏性Th2细胞反应的易感性更高。本综述重点介绍了目前对平衡Th2细胞对环境变应原免疫的因素的理解，特别关注促使传统树突状细胞（cDC）具有或不具有Th2刺激功能的决定因素。在此背景下，讨论了转录因子引导的2型cDC（cDC2）的功能特化，以及来自环境的信号整合如何驱动这一过程。此外，分析了支持空气传播变应原中所含微生物衍生产物的先天感知在调节过敏性Th2细胞免疫反应中起重要作用的观察性和机制性研究。最后，本综述探讨了对微生物刺激（特别是对LPS）低反应性是否是婴儿期和幼儿期诱导Th2细胞反应和过敏性致敏的危险因素，以及可能影响早期对LPS和其他环境微生物成分反应的潜在因素。
