Leptin/Osteopontin Axis Regulated Type 2T Helper Cell Response in Allergic Rhinitis with Obesity.
Leptin/Osteopontin Axis Regulated Type 2T Helper Cell Response in Allergic Rhinitis with Obesity.
复制标题
瘦素/骨桥蛋白轴调节 2T 型辅助细胞对肥胖过敏性鼻炎的反应。
DOI：
10.1016/j.ebiom.2018.05.037
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发表时间：
2018-06
期刊：
影响因子：
11.1
通讯作者：
Li H
中科院分区：
文献类型：
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作者：
Zeng Q;Luo X;Han M;Liu W;Li H
近几十年来，儿童变应性鼻炎（AR）和肥胖的患病率同时增加。然而，肥胖和AR之间相互作用的分子途径仍不清楚。本研究旨在探讨瘦素和骨桥蛋白（OPN）在儿童变应性鼻炎发病中的相互作用及其对辅助性T细胞（TH）反应的影响。30名AR和30名健康儿童（有或无肥胖）入组。检测血清瘦素、骨桥蛋白水平，并分析其与TH 1/2细胞因子的关系。采用酶联免疫吸附试验（ELISA）检测瘦素和/或骨桥蛋白（OPN）刺激的外周血单个核细胞（PBMC）中TH细胞分化和细胞因子产生。建立肥胖AR小鼠模型，以验证肥胖对瘦素和骨桥蛋白以及TH调节的影响。进行免疫沉淀以确认OPN和瘦素在CD 4 + T细胞中的相互作用。我们的研究结果表明，AR儿童血清瘦素和OPN升高与TH 2细胞因子表达相关。瘦素和OPN协同增强了屋尘螨刺激的AR儿童PBMC中的TH 2炎症。肥胖AR小鼠鼻黏膜炎症反应、症状及瘦素、骨桥蛋白表达均较其他组严重。免疫沉淀结果表明，OPN与瘦素之间可能存在相互作用，这一作用可能通过α4整合素和PI 3 K/AKT通路介导。我们的数据提供证据表明瘦素介导的OPN上调促进AR中的TH 2炎症，并且该过程通过α4整合素和PI 3 K/AKT信号通路实现。既往研究表明，瘦素和骨桥蛋白在变应性鼻炎患者中均升高，且与疾病严重程度相关。我们还提供了证据表明瘦素和骨桥蛋白有助于TH 2偏气道疾病。在本研究中，我们的数据表明，肥胖和过敏性鼻炎通过瘦素和OPN密切相互作用，这些细胞因子可能被用作过敏性鼻炎疾病严重程度的潜在生物标志物，尽管需要更多的研究。
The prevalence of allergic rhinitis (AR) and obesity in children increased concurrently during recent decades. However, the molecular pathway involved in the interaction between obesity and AR is still unclear. We aimed to investigate the interaction between leptin and osteopontin (OPN) and their effect on T helper (TH) response in the development of AR in children. Thirty AR and 30 healthy children with or without obesity were enrolled. Serum leptin and OPN levels were measured and their relationship with TH1/2 cytokines was analyzed. TH cell differentiation and cytokine production in peripheral blood mononuclear cells (PBMCs) stimulated by leptin and/or OPN were analyzed by enzyme linked immunosorbent assay (ELISA). Obese AR mice models were established to verify the effect of obesity on leptin and OPN as well TH regulation. Immunoprecipitation was performed to confirm the interaction between OPN and leptin in CD4+ T cells. Our results showed elevated serum leptin and OPN in AR children correlated with TH2 cytokines expression. Leptin and OPN enhanced TH2 inflammation in house dust mite stimulated PBMCs from AR children synergistically. Obese AR mice showed as more severe inflammatory reaction, symptoms and expression of nasal leptin and OPN compared with other groups. Immunoprecipitation suggested that OPN and leptin may interact with each other and this process may be mediated by α4 integrin and PI3K/AKT pathway in CD4+ T cells. Our data provide evidence that leptin-mediated OPN upregulation promote TH2 inflammation in AR and this process is achieved through the α4 integrin and PI3K/AKT signaling pathways. Previous studies suggested that both leptin and osteopontin are increased in allergic rhinitis patients and related to the severity of disease. We also provide evidence that leptin and osteopontin contributes to TH2-skewed airway diseases. In the present study, our data suggested that obesity and allergic rhinitis interacted closely through leptin and OPN, and these cytokines may be used as potential biomarkers for disease severity of allergic rhinitis despite that more studies were needed.
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影响因子：
4.4
作者：
Mai, Xiao-Mei;Chen, Yue;Krewski, Daniel
通讯作者：
Krewski, Daniel
影响因子：
14.2
作者：
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通讯作者：
Schuenemann, Holger J.
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作者：
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Marseglia, Gianluigi
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Huang, Shau-Ku
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82.9
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