House dust extracts have both TH2 adjuvant and tolerogenic activities
House dust extracts have both TH2 adjuvant and tolerogenic activities
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DOI：
10.1016/j.jaci.2006.03.025
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发表时间：
2006-05-01
影响因子：
14.2
通讯作者：
Horner, Anthony A.
中科院分区：
文献类型：
--
作者：
Ng, Nicholas;Lam, Diane;Horner, Anthony A.
背景资料：虽然机制仍然是一个有争议的主题，但人们普遍认为生活环境会影响生命最初几年的过敏风险。我们推断无菌屋尘提取物（HDES）具有反映其来源环境的免疫学活性，因此可作为研究环境暴露如何影响免疫稳态的有用替代物。目的：这些实验确定气道HDE暴露如何影响对共同施用抗原的适应性反应和随后对抗原激发的气道超敏反应。小鼠每周接受鼻内卵清蛋白（OVA）疫苗接种。选择组的小鼠也接受了鼻内HDE每周与OVA，每天在每周剂量的七分之一，开始前7天的第一个OVA敏化，或both.Results：每周鼻内接种，OVA和HDE引发小鼠的T（H）2偏向免疫和气道过敏反应的发展。相比之下，每日低剂量鼻内FIDE暴露保护免受与每周鼻内OVA/HDE疫苗接种相关的免疫学和病理学结果。发现HDE的T（H）2佐剂活性依赖于MyD 88，MyD 88是通过大多数Toll样受体进行信号传导的关键分子。此外，与每日鼻内HDE暴露相关的致耐受性活性可以用LPS.Conclusion复制：这些研究表明，除了过敏原，生活环境中含有具有T（H）2佐剂和致耐受性活性的免疫调节物质。由于HDE的内容物无处不在，这些实验可能概括并有助于解释与维持吸入性变应原耐受性和导致过敏反应的失调反应有关的临床相关免疫学事件。呼吸道疾病。
Background: Although mechanisms remain a subject of controversy, there is general agreement that living environments influence allergic risk during the first years of life. We reasoned that sterile house dust extracts (HDEs) would have immunologic activities reflective of their environments of origin and therefore would be useful surrogates for investigations of how ambient exposures influence immune homeostasis.Objective: These experiments determined how airway HDE exposures influence adaptive responses to a coadministered antigen and subsequent airway hypersensitivity responses to antigen challenge.Methods: Mice received intranasal ovalbumin (OVA) vaccinations on a weekly basis. Select groups of mice also received intranasal HDE weekly with OVA; daily at one seventh the weekly dose, beginning 7 days before the first OVA sensitization; or both.Results: Weekly intranasal vaccinations with,OVA and HDE primed mice for the development of T(H)2-biased immune and airway hypersensitivity responses. In contrast, daily low-dose intranasal FIDE exposures protected against the immunologic and pathologic outcomes associated with weekly intranasal OVA/HDE vaccinations. The T(H)2 adjuvant activities of HDEs were found to be dependant on MyD88, a molecule critical for signaling through a majority of Toll-like receptors. Moreover, the tolerogenic activity associated with daily intranasal HDE exposures could be replicated with LPS.Conclusion: These investigations demonstrate that in addition to allergens, living environments contain immunomodulatory materials with both T(H)2 adjuvant and tolerogenic activities.Clinical implications: As the contents of HDEs are ubiquitous, these experiments might recapitulate and help explain clinically relevant immunologic events involved in the maintenance of aeroallergen tolerance and the dysregulated responses that lead to allergic respiratory diseases.