Airway epithelial STAT3 inhibits allergic inflammation via upregulation of stearoyl-CoA desaturase 1
Airway epithelial STAT3 inhibits allergic inflammation via upregulation of stearoyl-CoA desaturase 1
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气道上皮 STAT3 通过上调硬脂酰辅酶 A 去饱和酶 1 抑制过敏性炎症
DOI：
10.1016/j.alit.2022.05.002
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发表时间：
2022
影响因子：
6.8
通讯作者：
Nakajima H.
中科院分区：
文献类型：
--
作者：
Nishimura N;Yokota M;Kurihara S;Iwata A;Kageyama T;Ito T;Saku A;Maezawa Y;Hirose K;Nakajima H.
背景资料：气道上皮细胞（AEC）通过发育和激活免疫细胞（包括Th 2细胞和ILC 2）在过敏性炎症的诱导和发展中起关键作用。最近的研究表明，在上皮细胞中表达的STAT 3可以保护肠道免受病原体的侵害，并维持肠道内的稳态。然而，STAT 3在气道上皮中的作用知之甚少。因此，我们试图阐明气道上皮细胞STAT 3在变应性气道inflammation.Methods的作用：过敏性气道炎症的诱导室内尘螨（HDM）提取物在多西环素诱导的AEC特异性STAT 3缺陷（STAT 3-cKO）小鼠和他们的遗传控制（STAT 3-WT）小鼠气管内给药。通过支气管肺泡灌洗液细胞的流式细胞术分析和肺的组织学分析来评估气道炎症。纯化的气道上皮细胞通过定量PCR和RNA测序（RNA-seq）进行分析。结果：与STAT 3-WT小鼠相比，HDM诱导的气道炎症在STAT 3-cKO小鼠中加重。RNA-seq分析显示，与HDM处理的STAT 3-cKO小鼠相比，编码硬脂酰辅酶A去饱和酶1的Scd 1在HDM处理的STAT 3-WT小鼠中最显著上调。值得注意的是，SCD 1抑制剂的施用加剧了HDM诱导的气道炎症。HDM处理的STAT 3-cKO小鼠和HDM处理的SCD 1受体注射小鼠的AEC共有45个差异表达基因（DEG）。DEG的基因富集分析显示，富集的本体簇包括脂肪酸生物合成过程和脂质生物合成过程的调节，提示STAT 3-SCD 1-脂质代谢轴参与了对过敏性炎症的抑制作用。结论：STAT 3在抑制HDM诱导的过敏性气道炎症中起重要作用，可能诱导SCD 1在AECs中的表达。
Background: Airway epithelial cells (AECs) play a crucial role in the induction and development of allergic inflammation through the development and activation of immune cells, including Th2 cells and ILC2s. Recent studies have revealed that STAT3 expressed in epithelial cells protects against pathogens and maintains homeostasis in the intestine. However, the roles of STAT3 in airway epithelium are poorly understood. Therefore, we sought to elucidate the roles of airway epithelial STAT3 in allergic airway inflammation.Methods: Allergic airway inflammation was induced by intratracheal administration of house dust mite (HDM) extract in doxycycline-induced AEC-specific STAT3-deficient (STAT3-cKO) mice and their genetic control (STAT3-WT) mice. Airway inflammation was evaluated by flow cytometric analysis of bronchoalveolar lavage fluid cells and histological analysis of the lung. Purified airway epithelial cells were analyzed by quantitative PCR and RNA-sequencing (RNA-seq).Results: HDM-induced airway inflammation was exacerbated in STAT3-cKO mice compared with STAT3-WT mice. RNA-seq analyses revealed that Scd1, coding stearoyl-CoA desaturase 1, was most significantly upregulated in HDM-treated STAT3-WT mice compared to HDM-treated STAT3-cKO mice. Notably, the administration of an SCD1 inhibitor exacerbated HDM-induced airway inflammation. AECs of HDM-treated STAT3-cKO mice and those of HDM-treated SCD1 inhibitor-injected mice shared 45 differentially expressed genes (DEGs). Gene enrichment analysis of the DEGs revealed that the enriched ontology clusters included fatty acid biosynthetic process and regulation of lipid biosynthetic process, suggesting the involvement of the STAT3-SCD1-lipid metabolism axis in suppressing allergic inflammation.Conclusions: STAT3 is crucial for suppressing HDM-induced allergic airway inflammation, possibly inducing SCD1 expression in AECs.