IL-17 regulates DC migration to the peribronchial LNs and allergen presentation in experimental allergic asthma
IL-17 regulates DC migration to the peribronchial LNs and allergen presentation in experimental allergic asthma
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DOI：
10.1002/eji.201948409
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发表时间：
2020-03-29
影响因子：
5.4
通讯作者：
Hansen, Gesine
中科院分区：
文献类型：
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作者：
Jirmo, Adan Chari;Busse, Mandy;Hansen, Gesine
IL-17与哮喘的不同表型相关，然而，它如何影响哮喘和过敏的诱导和维持尚未完全阐明。为了确定IL-17在变应性哮喘发展中的作用，我们在实验性变应性哮喘模型中使用IL-17 A/F双KO（IL-17 A/F KO）和WT小鼠（有或没有IL-17中和），并分析气道高反应性、肺部炎症、辅助性T细胞极化和DC内流和活化。我们报道了IL-17的缺乏减少了DC流入肺和肺引流淋巴结。与WT小鼠相比，IL-17 A/F KO小鼠或IL-17 A中和后的WT小鼠显示降低的气道高反应性、嗜酸性粒细胞增多症、粘液高分泌和IgE水平。与WT DC相比，来自变应原攻击的IL-17 A/F KO小鼠的引流LN的DC显示出迁移和共刺激分子CCR 7、CCR 2、MHC-II和CD 40的表达减少。此外，在不存在IL-17的情况下，过继转移的抗原特异性细胞的体内刺激在肺引流LN中减弱。因此，我们报道IL-17增强气道DC的活化、迁移和功能。因此，缺乏IL-17导致抗原特异性T细胞引发减少和实验性过敏性哮喘的发展受损。
IL-17 is associated with different phenotypes of asthma, however, it is not fully elucidated how it influences induction and maintenance of asthma and allergy. In order to determine the role of IL-17 in development of allergic asthma, we used IL-17A/F double KO (IL-17A/F KO) and WT mice with or without neutralization of IL-17 in an experimental allergic asthma model and analyzed airway hyperresponsiveness, lung inflammation, T helper cell polarization, and DCs influx and activation. We report that the absence of IL-17 reduced influx of DCs into lungs and lung draining LNs. Compared to WT mice, IL-17A/F KO mice or WT mice after neutralization of IL-17A showed reduced airway hyperresponsiveness, eosinophilia, mucus hypersecretion, and IgE levels. DCs from draining LNs of allergen-challenged IL-17A/F KO mice showed a reduction in expression of migratory and costimulatory molecules CCR7, CCR2, MHC-II, and CD40 compared to WT DCs. Moreover, in vivo stimulation of adoptively transferred antigen-specific cells was attenuated in lung-draining LNs in the absence of IL-17. Thus, we report that IL-17 enhances airway DC activation, migration, and function. Consequently, lack of IL-17 leads to reduced antigen-specific T cell priming and impaired development of experimental allergic asthma.