Hypoxia disrupts aryl hydrocarbon receptor signaling and the Th17 response in allergic rhinitis patients
Hypoxia disrupts aryl hydrocarbon receptor signaling and the Th17 response in allergic rhinitis patients
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缺氧会破坏过敏性鼻炎患者的芳基碳氢化合物受体信号传导和 Th17 反应
DOI：
10.1016/j.molimm.2018.07.025
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发表时间：
2018-09-01
影响因子：
3.6
通讯作者：
Wei, Ping
中科院分区：
文献类型：
--
作者：
Kou, Wei;Li, Xuelei;Wei, Ping
背景。缺氧条件是变应性鼻炎（AR）的关键特征，然而，缺氧在AR中的作用仍有待充分了解。本研究旨在通过研究缺氧影响的信号通路对Th17分化的作用，探讨缺氧对AR患者Th17反应的影响。方法：选取23例AR患者和15例健康对照者进行研究。在常氧和缺氧条件下，检测CD4(+) T细胞中HIF-1 α、AhR、CYP1A1和CYP1B1的表达以及Th17细胞的存在。此外，在2-（1h -吲哚-3-羰基）-4-噻唑羧酸甲酯（CITE）暴露于常氧和缺氧环境后，测定ARNT与HIF-1 α或AhR联合的量。结果：AR患者CD4(+) T细胞中HIF-1 α和AhR的表达高于健康对照组。在缺氧环境下，AR患者和健康对照者的CD4(+) T细胞中HIF-1 α的表达均升高。同时，在缺氧条件下，在AR患者和健康对照的细胞中，无毒AhR配体（CITE）对Th17反应的抑制作用及其对IL-10产生的积极作用被抑制。这些影响是由于HIF-1 α在ARNT结合方面胜过AhR，从而限制了AhR通路的活性。结论：目前的结果表明，缺氧能够通过HIF-1 α活性降低AhR活性来促进Th17反应。因此，缺氧可能与AR的发病机制密切相关。
Background. Hypoxic conditions area key feature of allergic rhinitis (AR), however, the role of hypoxia in AR remains to be fully understood. The aim of this study was to survey the effect of hypoxia on the Th17 response in AR patients by investigating the action of hypoxia-influenced signaling pathways on Th17 differentiation.Methods: 23 AR patients and 15 healthy controls were recruited for this study. Under normoxia and hypoxic conditions, the expression of HIF-1 alpha, AhR, CYP1A1 and CYP1B1 and the presence of Th17 cells in CD4(+) T cells were measured. Furthermore, the amount of ARNT combined with either HIF-1 alpha or AhR was determined after the exposure of 2-(1H-Indol-3-ylcarbonyl)-4-thiazolecarboxylic acid methyl easter CITE) with normoxia and hypoxia.Results: HIF-1 alpha and AhR expression were higher in CD4(+) T cells from AR patients than in those from healthy controls. In a hypoxic environment, the expression of HIF-1 alpha was elevated in CD4(+) T cells of both AR patients and healthy controls. Meanwhile, the suppressive effects of a non-toxic AhR ligand CITE) on the Th17 response and its positive effects on IL-10 production were suppressed in the cells of AR patients and healthy controls under hypoxia. These effects were arisen from HIF-1 alpha out-competing AhR for ARNT binding which limited the activity of the AhR pathway.Conclusions: The present results suggest that hypoxia is capable of promoting the Th17 response by reducing AhR activity via HIF-1 alpha activity. Thus hypoxia may be intimately involved in the pathogenesis of AR.