The danger signal, extracellular ATP, is a sensor for an airborne allergen and triggers IL-33 release and innate Th2-type responses.
The danger signal, extracellular ATP, is a sensor for an airborne allergen and triggers IL-33 release and innate Th2-type responses.
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DOI：
10.4049/jimmunol.1003020
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发表时间：
2011-04-01
期刊：
影响因子：
--
通讯作者：
Kita H
中科院分区：
文献类型：
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作者：
Kouzaki H;Iijima K;Kobayashi T;O'Grady SM;Kita H
气道中先天性和适应性促过敏Th2型反应起始的分子机制尚未完全明确。白细胞介素 - 33（IL - 33）是白细胞介素 - 1家族分子的新成员，与Th2型反应有关。将未致敏小鼠的气道暴露于一种常见的环境气传过敏原——链格孢菌，会诱导IL - 33迅速释放到气道腔内，随后引发先天性Th2型反应。具有生物活性的IL - 33在人呼吸道上皮细胞的细胞核中组成性储存。将这些上皮细胞在体外暴露于链格孢菌会使IL - 33释放到细胞外。过敏原暴露还会诱导一种危险信号——三磷酸腺苷（ATP）在细胞外急性积聚；这种自分泌的ATP通过激活P2嘌呤能受体维持细胞内钙离子浓度升高并释放IL - 33。嘌呤能受体的药理抑制剂或P2Y2基因缺失可消除未致敏小鼠在链格孢菌诱导的气道炎症模型中IL - 33的释放和Th2型反应，这强调了ATP和P2Y2受体的重要作用。因此，呼吸道上皮中的ATP和嘌呤能信号传导是气道暴露于气传过敏原的关键感受器，它们可能为抑制Th2型气道疾病（如哮喘）的过敏反应提供新的契机。
The molecular mechanisms underlying the initiation of innate and adaptive proallergic Th2-type responses in the airways are not well understood. IL-33 is a new member of the IL-1 family molecules that is implicated in Th2-type responses. Airway exposure of naïve mice to a common environmental aeroallergen, the fungus Alternaria alternata, induces rapid release of IL-33 into the airway lumen, followed by innate Th2-type responses. Biologically-active IL-33 is constitutively stored in the nuclei of human airway epithelial cells. Exposing these epithelial cells to Alternaria alternata releases IL-33 extracellularly in vitro. Allergen exposure also induces acute extracellular accumulation of a danger signal, ATP; this autocrine ATP sustains increases in intracellular Ca2+ concentration and releases IL-33 through activation of P2 purinergic receptors. Pharmacological inhibitors of purinergic receptors or deficiency in the P2Y2 gene abrogate IL-33 release and Th2-type responses in the Alternaria-induced airway inflammation model in naïve mice, emphasizing the essential roles for ATP and the P2Y2 receptor. Thus, ATP and purinergic signaling in the respiratory epithelium are critical sensors for airway exposure to airborne allergens, and they may provide novel opportunities to dampen the hypersensitivity response in Th2-type airway diseases, such as asthma.
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DOI：
10.1073/pnas.0812690106
发表时间：
2009-06-02
影响因子：
11.1
作者：
Cayrol, Corinne;Girard, Jean-Philippe
通讯作者：
Girard, Jean-Philippe
影响因子：
30.8
作者：
Gudbjartsson, Daniel F.;Bjornsdottir, Unnur S.;Stefansson, Kari
通讯作者：
Stefansson, Kari
影响因子：
5.5
作者：
Gudipaty, L;Munetz, J;Dubyak, GR
通讯作者：
Dubyak, GR
影响因子：
6
作者：
Baekkevold, ES;Roussigné, M;Girard, JP
通讯作者：
Girard, JP
影响因子：
30.5
作者：
通讯作者：
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