Treatment of allergic rhinitis with CpG oligodeoxynucleotides alleviates the lower airway outcomes of combined allergic rhinitis and asthma syndrome via a mechanism that possibly involves in TSLP
Treatment of allergic rhinitis with CpG oligodeoxynucleotides alleviates the lower airway outcomes of combined allergic rhinitis and asthma syndrome via a mechanism that possibly involves in TSLP
复制标题
使用 CpG 寡脱氧核苷酸治疗过敏性鼻炎可通过可能涉及 TSLP 的机制减轻过敏性鼻炎和哮喘联合综合征的下气道结果
DOI：
10.1080/01902148.2016.1215571
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发表时间：
2016-01-01
影响因子：
1.7
通讯作者：
Zhang, Tian-tuo
中科院分区：
文献类型：
--
作者：
Li, Hong-tao;Chen, Zhuang-gui;Zhang, Tian-tuo
目的：胸腺基质淋巴生成素（TSLP）是与Th2细胞因子介导的炎症相关的免疫反应的关键调节因子。鼻内给药具有CpG基序的寡脱氧核苷酸（CpG- odns）可能改善合并变应性鼻炎和哮喘综合征（CARAS）的下气道结局，但CpG- odns的内在机制尚不明确。本研究探讨了CpG-ODNs处理上呼吸道是否可以降低下气道TSLP的表达，以及这种降低是否有助于减轻CARASmice的下气道过敏性炎症和气道高反应性（AHR）。材料与方法：卵清蛋白（OVA）致敏BALB/c小鼠，每周鼻内暴露OVA 3次，持续3周。将CpG-ODNs或抗tslp单抗给予这些小鼠的一部分，在鼻内注射OVA 1小时后，随后进行5天的OVA气溶胶注射。评估由此产生的免疫学变量、鼻症状、鼻黏膜和肺组织病理。采用RT-PCR、western blotting或酶联免疫吸附法检测肺组织和支气管肺泡灌洗液（BALF）中TSLP的产生。结果：CARAS小鼠在肺组织和BALF中表现出TSLP的过表达，BALF和脾细胞th2相关细胞因子的产生、血清ova特异性IgE、鼻和肺病理以及AHR均显著升高。经鼻给药CpG-ODNs可恢复下气道TSLP，并显著降低以下参数：th2型细胞因子产生水平；BALF中嗜酸性粒细胞的百分比；脾淋巴细胞培养上清液中IL-4、IL-5的含量；血清ova特异性IgE；肺部支气管周围炎症评分；鼻子病理和鼻症状。当CARAS小鼠用抗TSLP单抗阻断鼻内TSLP活性时，获得了类似的结果。结论：经鼻CpG-ODNs治疗可改善CARAS模型下气道免疫可变结果，其机制可能涉及抑制肺tslp引发的过敏性炎症。
Purpose: Thymic stromal lymphopoietin (TSLP) is a critical regulator of immune responses associated with Th2 cytokine-mediated inflammation. Intranasal administration of oligodeoxynucleotides with CpG motifs (CpG-ODNs) might improve lower airway outcomes of combined allergic rhinitis and asthma syndrome (CARAS), but the inherent mechanisms of CpG-ODNs are not well defined. This study investigated whether CpG-ODNs treated to upper airway could reduce lower airway TSLP expression aswell as whether this reduction could contribute to the alleviation of lower allergic inflammation and airway hyper-reactivity (AHR) in CARASmice. Materials andMethods: Ovalbumin (OVA)sensitized BALB/c mice were intranasal OVA exposure three times a week for 3 weeks. CpG-ODNs or an anti-TSLP mAb was administered to a subset of these mice 1 hour after intranasal OVA challenge, followed by 5 days of OVA aerosol challenge. The resulting immunological variables, nasal symptoms, and nasal mucosa and lung tissues pathology were evaluated. TSLP production in the lung tissues and bronchoalveolar lavage fluid (BALF) were determined by RT-PCR, western blotting or enzymelinked immunosorbent assay. Results: The CARAS mice exhibited overexpression of TSLP in the lung tissues and BALF, and also demonstrated significant increases in BALF and splenocyte Th2-associated cytokine production, serum OVA-specific IgE, nose and lung pathologies, and AHR. Intranasal administration of CpG-ODNs restored TSLP in the lower airway, and it significantly reduced the following parameters: Th2-type cytokine production levels; the percentage of eosinophils in the BALF; IL-4 and IL-5 concentrations in the supernatants of cultured splenic lymphocytes; serum OVA-specific IgE; peribronchial inflammation score in the lungs; and nose pathology and nasal symptoms. Similar results were obtained when the CARAS mice were treated with an anti-TSLP mAb to block intranasal TSLP activity. Conclusions: Treatment with intranasal CpG-ODNs improves lower airway immunological variable outcomes in the CARAS model via a mechanism that possibly involves in suppressing pulmonary TSLP-triggered allergic inflammation.