School of Paediatrics and Child Health Research, University of Western Australia, Perth, WA, Australia.
School of Paediatrics and Child Health Research, University of Western Australia, Perth, WA, Australia.
Chest. 2011 Mar;139(3):640-647. doi: 10.1378/chest.10-1800.
Uterine life is arguably the most critical time in developmental programming, when environmental exposures may have the greatest potential to influence evolving fetal structure and function. There has been substantial progress in understanding the epigenetic mechanisms through which environmental exposures can permanently alter the expression of fetal genes and contribute to the increasing propensity for many complex diseases. These concepts of "developmental origins" of disease are being applied across virtually all fields of medicine, and emerging epigenetic paradigms are the likely mechanism behind the environment-driven epidemic of asthma and allergic disease. Here, we examine the epigenetic regulation of immune development and the early immune profiles that contribute to allergic risk. In particular we review new evidence that key environmental exposures, such as microbial exposure, dietary changes, tobacco smoke, and pollutants, can induce epigenetic changes in gene expression and alter disease risk. Although most of these factors have already been clearly implicated in epidemiologic studies of asthma and allergic disease, new studies investigating the mechanisms of these effects may provide new avenues for using these pathways for disease prevention.
子宫内的生命阶段可以说是发育编程中最为关键的时期，在此期间，环境暴露可能对不断发育的胎儿结构和功能产生最大的影响。人们在理解环境暴露如何通过表观遗传机制永久性改变胎儿基因的表达，从而增加许多复杂疾病的易感性方面已经取得了重大进展。这些“疾病发育起源”的概念几乎适用于医学的所有领域，新兴的表观遗传范例可能是哮喘和过敏性疾病环境驱动流行背后的机制。在这里，我们研究了免疫发育的表观遗传调控以及导致过敏风险的早期免疫特征。特别是，我们回顾了新的证据，表明关键的环境暴露，如微生物暴露、饮食变化、烟草烟雾和污染物，可诱导基因表达的表观遗传变化，并改变疾病风险。尽管这些因素中的大多数已经在哮喘和过敏性疾病的流行病学研究中明确涉及，但新的研究调查这些影响的机制可能为利用这些途径预防疾病提供新的途径。
