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The common γ-chain cytokine IL-7 promotes immunopathogenesis during fungal asthma.
Mucosal Immunology ( IF 8 ) Pub Date : 2018-09-01 , DOI: 10.1038/s41385-018-0028-1
Kristen M Reeder 1 , Chad W Dunaway 1 , Jonathan P Blackburn 1 , Zhihong Yu 2 , Sadis Matalon 2 , Annette T Hastie 3 , Elizabeth J Ampleford 3 , Deborah A Meyers 4 , Chad Steele 1
Affiliation  

Asthmatics sensitized to fungi are reported to have more severe asthma, yet the immunopathogenic pathways contributing to this severity have not been identified. In a pilot assessment of human asthmatics, those subjects sensitized to fungi demonstrated elevated levels of the common γ-chain cytokine IL-7 in lung lavage fluid, which negatively correlated with the lung function measurement PC20. Subsequently, we show that IL-7 administration during experimental fungal asthma worsened lung function and increased the levels of type 2 cytokines (IL-4, IL-5, IL-13), proallergic chemokines (CCL17, CCL22) and proinflammatory cytokines (IL-1α, IL-1β). Intriguingly, IL-7 administration also increased IL-22, which we have previously reported to drive immunopathogenic responses in experimental fungal asthma. Employing IL22CreR26ReYFP reporter mice, we identified γδ T cells, iNKT cells, CD4 T cells and ILC3s as sources of IL-22 during fungal asthma; however, only iNKT cells were significantly increased after IL-7 administration. IL-7-induced immunopathogenesis required both type 2 and IL-22 responses. Blockade of IL-7Rα in vivo resulted in attenuated IL-22 production, lower CCL22 levels, decreased iNKT cell, CD4 T-cell and eosinophil recruitment, yet paradoxically increased dynamic lung resistance. Collectively, these results suggest a complex role for IL-7 signaling in allergic fungal asthma.

中文翻译:

常见的 γ 链细胞因子 IL-7 促进真菌性哮喘期间的免疫发病机制。

据报道,对真菌敏感的哮喘患者患有更严重的哮喘,但导致这种严重程度的免疫致病途径尚未确定。在对人类哮喘患者的初步评估中,那些对真菌敏感的受试者表现出肺灌洗液中常见 γ 链细胞因子 IL-7 水平升高,这与肺功能测量 PC20 呈负相关。随后,我们发现,在实验性真菌哮喘期间给予 IL-7 会恶化肺功能,并增加 2 型细胞因子(IL-4、IL-5、IL-13)、促过敏趋化因子(CCL17、CCL22)和促炎细胞因子(IL)的水平。 -1α、IL-1β)。有趣的是,IL-7 给药还增加了 IL-22,我们之前曾报道过 IL-22 可驱动实验性真菌哮喘中的免疫致病反应。使用 IL22 CreR26R eYFP报告小鼠,我们确定 γδ T 细胞、iNKT 细胞、CD4 T 细胞和 ILC3 是真菌哮喘期间 IL-22 的来源;然而,IL-7给药后只有iNKT细胞显着增加。IL-7 诱导的免疫发病机制需要 2 型和 IL-22 反应。体内阻断 IL-7Rα 会导致 IL-22 产生减弱,CCL22 水平降低,iNKT 细胞、CD4 T 细胞和嗜酸性粒细胞募集减少,但矛盾的是动态肺阻力增加。总的来说,这些结果表明 IL-7 信号在过敏性真菌哮喘中发挥着复杂的作用。
更新日期:2018-06-16
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