胸腺基质淋巴细胞生成素
过敏性炎症
免疫学
FOXP3型
炎症
细胞因子
RAR相关孤儿受体γ
结膜
过敏性结膜炎
白细胞介素
污渍
医学
免疫系统
生物
过敏
基因
生物化学
作者
Xin Chen,Ran Deng,Wei Chi,Xin Hua,Fan Liu,Fang Bian,Ning Gao,Zhijie Li,Stephen C. Pflugfelder,Cintia S. de Paiva,Dequan Li
出处
期刊:Allergy
[Wiley]
日期:2019-01-04
卷期号:74 (5): 910-921
被引量:30
摘要
Abstract Background While 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. Methods A murine model of experimental allergic conjunctivitis ( EAC ) was induced in BALB /c, C57 BL /6 or IL ‐27Rα‐deficient ( WSX ‐1 −/− ) mice by short ragweed pollen, with untreated or PBS ‐treated mice as controls. The serum, eyeballs, conjunctiva, cervical lymph nodes ( CLN s) were used for study. Gene expression was determined by RT ‐ qPCR , and protein production and activation were evaluated by immunostaining, ELISA and Western blotting. Results Typical allergic manifestations and stimulated thymic stromal lymphopoietin ( TSLP ) signaling and Th2 responses were observed in ocular surface of EAC models in BALB /c and C57 BL /6 mice. The decrease of IL ‐27 at mRNA ( IL ‐27/ EBI 3) 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 ROR γt. In contrast, Th1 cytokine IFN γ and Treg marker IL ‐10, with their respective transcription factors T‐bet and foxp3, were largely suppressed. Interestingly, imbalanced activation between reduced phosphor (P)‐ STAT 1 and stimulated P‐ STAT 6 were revealed in EAC , especially WSX ‐1 −/− ‐ EAC mice. Conclusion These 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.
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