影响过敏发展的早期生活因素

Early life factors that affect allergy development

doi: 10.1038/nri.2017.39

这是最新一期Nature Reviews Immunology[IF：39.932]上发表的关于影响过敏发展的生命早期因素的必读综述，最近这方面综述很多，有爆发之势头，相关知识出得比较集中，但这篇仍然值得精读必读！强烈推荐！

论文摘要

Allergy is characterized by an inappropriate immune response to one or several foreign antigens, and this response can give rise to conditions such as aller- gic asthma, food allergy, atopic dermatitis (eczema), allergic rhinitis (hay fever) and anaphylaxis. Individuals with an allergy typically produce high levels of IgE in response to allergen exposure (that is, an atopic response), although allergic responses that are not mediated by IgE (that is, non-atopic responses) can also occur1. Many allergies first present in childhood, and there are several common sources of allergens (BOX 1). Often, childhood food allergies spontaneously resolve by late childhood, although sensitivity to certain allergens, such as peanuts or tree nuts, is more likely to persist into adulthood2. The severity of the childhood symptoms of allergic asthma is a predictor of disease persistence into adulthood3. 

Type 2 immune responses are central to the develop- ment of an allergic response. Following mucosal tissue damage and allergen exposure, epithelial cells release the cytokines thymic stromal lymphopoietin (TSLP), interleukin-25 (IL-25) and IL-33. These cytokines ini- tiate a type 2 response by recruiting eosinophils and basophils, activating B cells and dendritic cells (DCs), and promoting the differentiation of type 2 innate lym- phoid cells (ILC2s) and T helper 2 (TH2) cells4. The production of IL-4, IL-5, IL-9 and IL-13 by ILC2s and TH2 cells can stimulate several type 2 effector responses that are hallmarks of allergy: specifically, IL-4 from TH2 cells can promote B cell isotype class-switching to IgE; IL-5 and IL-9 can promote the recruitment of eosino- phils and mast cells; and IL-13 can stimulate mucus hypersecretion and airway hyper-reactivity5. Secreted antigen-specific IgE can bind to high-affinity Fcε recep- tors on basophils and mast cells, and these receptors mediate their degranulation upon subsequent antigen exposure. Granulocyte degranulation releases inflam-matory mediators that can cause airway contractility and increased vascular permeability, and promote the recruitment of additional inflammatory cells6. In contrast to pathways that lead to allergic sensitization, either local or systemic tolerance to potential allergens can occur. Tolerance can be achieved through lymphocyte anergy or through the suppressive actions of several regulatory populations, of which the best characterized are the followingregulatory T cell (T cell) subsets: forkhead box protein P3 reg (FOXP3)-expressing CD4+ T cells and IL-10-producing FOXP3−CD4+ T regulatory type 1 (TR1) cells7,8.

实验综述

① 出生后首月接触的环境因素影响过敏风险；

② 常见食物过敏源有花生、牛奶、鸡蛋，吸入性过敏源有花粉、动物皮屑、尘螨、蟑螂、真菌；

③ 皮肤抗原暴露引起Th2细胞反应导致变应性致敏，肠道粘膜抗原暴露更易诱导耐受性反应；

④ 生命早期较早地接触抗原，与较低的过敏风险相关；

⑤ 许多细菌可通过限制Th2型细胞因子（IL-4、IL-13）或刺激B细胞的MYD88信号控制循环IgE水平。⑥ 早期感染不同病原体，可恶化过敏性疾病，也可促进免疫耐受。