GM-CSF produced by the airway epithelium is required for sensitization to cockroach allergen.
GM-CSF produced by the airway epithelium is required for sensitization to cockroach allergen.
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DOI：
10.1038/mi.2016.90
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发表时间：
2017-05
影响因子：
8
通讯作者：
Ziegler SF
中科院分区：
文献类型：
--
作者：
Sheih A;Parks WC;Ziegler SF
气道上皮细胞是最先遇到吸入性过敏原的细胞之一，并可通过产生pro-Th 2先天性细胞因子来启动过敏反应。在这项研究中，我们研究了上皮细胞衍生的细胞因子在致敏的临床相关的过敏原，蟑螂过敏原（CRA）的作用。在上皮细胞源性细胞因子中，GM-CSF在启动对CRA的Th 2变态反应中起核心作用。我们发现，最初暴露于CRA直接激活气道上皮细胞通过TLR 4-MyD 88依赖性途径和MyD 88在上皮细胞中的信号转导诱导GM-CSF在致敏过程中上调。上皮来源的GM-CSF是过敏性致敏所必需的，并且在MyD 88不存在的情况下选择性地恢复Th 2应答。因此，我们证明，上皮来源的GM-CSF是一个关键的早期信号在过敏致敏CRA。
Airway epithelial cells are among the first to encounter inhaled allergens and can initiate allergic responses by producing pro-Th2 innate cytokines. In this study, we investigated the role of epithelial-derived cytokines in sensitization to a clinically relevant allergen, cockroach allergen (CRA). Among the epithelial-derived cytokines, GM-CSF played a central role in the initiation of Th2 allergic responses to CRA. We show that initial exposure to CRA directly activated airway epithelial cells through a TLR4-MyD88-dependent pathway and MyD88 signaling in epithelial cells induced upregulation of GM-CSF during sensitization. Epithelial-derived GM-CSF was required for allergic sensitization and selectively restored Th2 responses in the absence of MyD88. Thus, we demonstrate that epithelial-derived GM-CSF is a critical early signal during allergic sensitization to CRA.