Section on Developmental Genetics, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver NICHD, National Institutes of Health, Bethesda, Maryland 20892-1830, USA.
J Biol Chem. 2011 Sep 23;286(38):32883-9. doi: 10.1074/jbc.R110.197046. Epub 2011 Jul 28.
Allergic asthma is a chronic airway inflammatory disease in which exposure to allergens causes intermittent attacks of breathlessness, airway hyper-reactivity, wheezing, and coughing. Allergic asthma has been called a "syndrome" resulting from a complex interplay between genetic and environmental factors. Worldwide, >300 million individuals are affected by this disease, and in the United States alone, it is estimated that >35 million people, mostly children, suffer from asthma. Although animal models, linkage analyses, and genome-wide association studies have identified numerous candidate genes, a solid definition of allergic asthma has not yet emerged; however, such studies have contributed to our understanding of the multiple pathways to this syndrome. In contrast with animal models, in which T-helper 2 (T(H)2) cell response is the dominant feature, in human asthma, an initial exposure to allergen results in T(H)2 cell-dependent stimulation of the immune response that mediates the production of IgE and cytokines. Re-exposure to allergen then activates mast cells, which release mediators such as histamines and leukotrienes that recruit other cells, including T(H)2 cells, which mediate the inflammatory response in the lungs. In this minireview, we discuss the current understanding of how associated genetic and environmental factors increase the complexity of allergic asthma and the challenges allergic asthma poses for the development of novel approaches to effective treatment and prevention.
过敏性哮喘是一种慢性气道炎症性疾病，其特征为过敏原暴露可引起间歇性呼吸困难、气道高反应性、喘息和咳嗽。过敏性哮喘被称为一种“综合征”，是由遗传和环境因素之间复杂相互作用引起的。全世界有超过 3 亿人受到这种疾病的影响，仅在美国，据估计就有超过 3500 万人，主要是儿童，患有哮喘。尽管动物模型、连锁分析和全基因组关联研究已经确定了许多候选基因，但仍未对过敏性哮喘给出明确的定义；然而，这些研究有助于我们了解该综合征的多种途径。与动物模型中 T 辅助细胞 2（T(H)2）细胞反应占主导地位不同，人类哮喘中，最初接触过敏原会导致 T(H)2 细胞依赖性免疫反应刺激，介导 IgE 和细胞因子的产生。再次接触过敏原会激活肥大细胞，释放组胺和白三烯等介质，招募其他细胞，包括 T(H)2 细胞，介导肺部炎症反应。在这篇简评中，我们讨论了目前对相关遗传和环境因素如何增加过敏性哮喘复杂性的理解，以及过敏性哮喘对开发有效治疗和预防新方法提出的挑战。
