IL-33 and thymic stromal lymphopoietin mediate immune pathology in response to chronic airborne allergen exposure.
IL-33 and thymic stromal lymphopoietin mediate immune pathology in response to chronic airborne allergen exposure.
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DOI：
10.4049/jimmunol.1302984
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发表时间：
2014-08-15
期刊：
影响因子：
--
通讯作者：
Kita H
中科院分区：
文献类型：
--
作者：
Iijima K;Kobayashi T;Hara K;Kephart GM;Ziegler SF;McKenzie AN;Kita H
人类经常暴露在大气环境中的各种空气传播的过敏原中。这些过敏原可能会在呼吸道中触发复杂的免疫反应网络，导致哮喘和其他慢性呼吸道疾病。在这里，我们研究了慢性暴露于多种空气传播的过敏原引起的病理变化的免疫学机制。幼稚的小鼠被鼻内暴露于常见的空气传播过敏原的组合中，包括屋尘螨、交链孢子菌和曲霉菌，长达8周。这些变应原在4周内协同作用，诱导强烈的嗜酸性气道炎症、特异性IgE抗体产生、2型细胞因子反应和气道高反应性(AHR)，随后在8周内发生气道重塑。肺内T细胞、B细胞和2型固有淋巴样细胞(ILC2s)的浸润增加。CD4+T细胞和ILC2s参与了IL-5和IL-13的来源，提示先天免疫和获得性免疫都参与了这一模型。肺中IL-33水平在接触变应原后的几个小时内迅速升高，并在炎症的整个慢性期持续升高。IL-33受体(IL-33受体−/−)和TSLP受体(Tslpr−/−)缺陷小鼠的气道炎症、抗体水平和气道高反应性显著降低。相比之下，IL-25受体或IL-1受体缺陷的小鼠与野生型动物相比差异很小。因此，慢性暴露于天然空气传播的过敏原会触发一系列先天的和适应性的2型免疫反应和呼吸道病理，而IL-33和TSLP可能在这一过程中发挥关键作用。
Humans are frequently exposed to various airborne allergens in the atmospheric environment. These allergens may trigger a complex network of immune responses in the airways, resulting in asthma and other chronic airway diseases. Here, we investigated the immunological mechanisms involved in the pathological changes induced by chronic exposure to multiple airborne allergens. Naïve mice were exposed intranasally to a combination of common airborne allergens, including the house dust mite, Alternaria, and Aspergillus, for up to 8 weeks. These allergens acted synergistically and induced robust eosinophilic airway inflammation, specific IgE antibody production, type 2 cytokine response and airway hyperreactivity (AHR) in 4 weeks, followed by airway remodeling in 8 weeks. Increased lung infiltration of T cells, B cells, and type 2 innate lymphoid cells (ILC2s) was observed. CD4+ T cells and ILC2s contributed to the sources of IL-5 and IL-13, suggesting involvement of both innate and adaptive immunity in this model. The lung levels of IL-33 increased quickly within several hours after allergen exposure and continued to rise throughout the chronic phase of inflammation. Mice deficient in IL-33 receptor (Il1rl1−/−) and TSLP receptor (Tslpr−/−) showed significant reduction in airway inflammation, IgE antibody levels and AHR. In contrast, mice deficient in IL-25 receptor or IL-1 receptor showed minimal differences as compared to wild-type animals. Thus, chronic exposure to natural airborne allergens triggers a network of innate and adaptive type 2 immune responses and airway pathology, and IL-33 and TSLP likely play key roles in this process.
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DOI：
10.4049/jimmunol.1003020
发表时间：
2011-04-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kouzaki H;Iijima K;Kobayashi T;O'Grady SM;Kita H
通讯作者：
Kita H
DOI：
10.4049/jimmunol.1101632
发表时间：
2012-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Doherty TA;Khorram N;Sugimoto K;Sheppard D;Rosenthal P;Cho JY;Pham A;Miller M;Croft M;Broide DH
通讯作者：
Broide DH
影响因子：
32.4
作者：
Halim, Timotheus Y. F.;Krauss, Ramona H.;Takei, Fumio
通讯作者：
Takei, Fumio
影响因子：
14.2
作者：
Barlow, Jillian L.;Bellosi, Agustin;McKenzie, Andrew N. J.
通讯作者：
McKenzie, Andrew N. J.
影响因子：
14.2
作者：
Barlow, Jillian L.;Peel, Samantha;McKenzie, Andrew N. J.
通讯作者：
McKenzie, Andrew N. J.