IL-27 signaling deficiency develops Th17-enhanced Th2-dominant inflammation in murine allergic conjunctivitis model
IL-27 signaling deficiency develops Th17-enhanced Th2-dominant inflammation in murine allergic conjunctivitis model
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DOI：
10.1111/all.13691
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发表时间：
2019-05-01
期刊：
影响因子：
12.4
通讯作者：
Li, De-Quan
中科院分区：
文献类型：
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作者：
Chen, Xin;Deng, Ruzhi;Li, De-Quan
背景虽然大多数研究集中在促过敏细胞因子，免疫抑制细胞因子在过敏性炎症中的保护作用还没有得到很好的阐明。方法用豚草花粉诱导BALB/c、C57 BL/6和IL-27 R缺陷（WSX-1（-/-））小鼠实验性变应性结膜炎（EAC）模型，并设对照组和PBS处理组。采用血清、眼球、结膜、颈淋巴结（CLN）进行研究。通过RT-qPCR测定基因表达，并通过免疫染色，ELISA和Western blotting. ResultsDetermined蛋白质的生产和激活进行了评估。结果典型的过敏性表现和刺激的胸腺基质淋巴细胞生成素（TSLP）信号和Th 2反应观察EAC模型在BALB/c和C57 BL/6小鼠的眼表。通过RT-qPCR、免疫荧光染色、ELISA和Western印迹法评价，在血清、结膜和CLN中检测到IL-27在mRNA（IL-27/EBI 3）和蛋白水平上的降低。在WSX-1（-/-）小鼠中诱导的EAC显示出加重的过敏体征，伴有更高的TSLP驱动的Th 2-显性炎症，伴随刺激的Th 17应答，包括IL-17 A、IL-17 F和转录因子RORt。相反，Th 1细胞因子IFN和Treg标记物IL-10及其各自的转录因子T-bet和foxp 3在很大程度上受到抑制。有趣的是，在EAC中，尤其是WSX-1（-/-）-EAC小鼠中，P-STAT 1和P-STAT 6的激活不平衡。结论这些发现表明IL-27的天然保护机制，其中信号传导缺陷发展了Th 17型超应答，进一步加剧了Th 2型显性过敏性炎症。
BackgroundWhile most studies focus on pro-allergic cytokines, the protective role of immunosuppressive cytokines in allergic inflammation is not well elucidated. This study was to explore a novel anti-inflammatory role and cellular/molecular mechanism of IL-27 in allergic inflammation.MethodsA murine model of experimental allergic conjunctivitis (EAC) was induced in BALB/c, C57BL/6 or IL-27R-deficient (WSX-1(-/-)) mice by short ragweed pollen, with untreated or PBS-treated mice as controls. The serum, eyeballs, conjunctiva, cervical lymph nodes (CLNs) were used for study. Gene expression was determined by RT-qPCR, and protein production and activation were evaluated by immunostaining, ELISA and Western blotting.ResultsTypical allergic manifestations and stimulated thymic stromal lymphopoietin (TSLP) signaling and Th2 responses were observed in ocular surface of EAC models in BALB/c and C57BL/6 mice. The decrease of IL-27 at mRNA (IL-27/EBI3) and protein levels were detected in serum, conjunctiva and CLN, as evaluated by RT-qPCR, immunofluorescent staining, ELISA and Western blotting. EAC induced in WSX-1(-/-) mice showed aggravated allergic signs with higher TSLP-driven Th2-dominant inflammation, accompanied by stimulated Th17 responses, including IL-17A, IL-17F, and transcription factor RORt. In contrast, Th1 cytokine IFN and Treg marker IL-10, with their respective transcription factors T-bet and foxp3, were largely suppressed. Interestingly, imbalanced activation between reduced phosphor (P)-STAT1 and stimulated P-STAT6 were revealed in EAC, especially WSX-1(-/-)-EAC mice.ConclusionThese findings demonstrated a natural protective mechanism by IL-27, of which signaling deficiency develops a Th17-type hyperresponse that further aggravates Th2-dominant allergic inflammation.