Enhanced allergic airway disease in old mice is associated with a Th17 response
Enhanced allergic airway disease in old mice is associated with a Th17 response
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DOI：
10.1111/cea.12388
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发表时间：
2014-10-01
影响因子：
6.1
通讯作者：
Harkema, J. R.
中科院分区：
文献类型：
--
作者：
Brandenberger, C.;Li, N.;Harkema, J. R.
研究背景老年人哮喘的患病率正在增加，与儿童或年轻人相比，老年人哮喘的死亡率更高。然而，年龄对过敏性哮喘的发展和特征的影响尚未得到充分研究。已经表明混合的Th 2/Th 17应答导致更严重形式的哮喘，目的探讨小鼠屋尘螨（HDM）-变应原模型中变应性气道疾病的年龄依赖性特征和Th 17免疫应答。方法分别对15周龄和15月龄雄性BALB/c小鼠进行实验，c小鼠用HDM致敏和激发。检测支气管肺泡灌洗液（BALF）、气道炎症和高反应性（AHR）、血清免疫球蛋白和脾脏T细胞。与骨髓来源的树突状细胞（BMDC）和脾脏CD 4（+）T细胞从年轻和老年mice.ResultsFeatures变应性气道疾病，如粘液细胞增生，气道嗜酸性粒细胞和淋巴细胞浸润，Th 2细胞因子的表达和血清IgG 1水平的共同培养中分析的T细胞活化在老年人相比，年轻小鼠。与老年小鼠对HDM的更显著的炎症/免疫反应相反，年轻HDM治疗小鼠的AHR更大。只有老年小鼠在HDM暴露后出现气道中性粒细胞浸润和Th 17免疫应答，BALF细胞因子IL-17 A和KC以及脾脏中产生Th 17细胞因子的T细胞增加。刺激CD 4（+）T细胞和BMDC与HDM共培养，导致从老年小鼠分离的细胞中Th 17细胞因子应答增强。结论和临床意义我们在小鼠中的发现表明，过敏性气道疾病的严重程度和特征是年龄依赖性的，随着年龄的增长，Th 17免疫应答偏向。老年哮喘患者可能容易发展为严重的过敏性气道炎症，伴有混合的Th 2/Th 17免疫应答。
BackgroundThe prevalence of asthma in the elderly is increasing and associated with higher mortality than in children or young adults. However, the effects of age on the development and character of allergic asthma have been understudied. It has been suggested that mixed Th2/Th17 responses cause more severe forms of asthma, but the role of Th17 response in allergic airway disease and aging is not well understood.ObjectiveTo investigate age-dependent characteristics and Th17 immune response in allergic airway disease in a murine house dust mite (HDM)-allergen model.MethodsTwelve-week-old and 15-month-old male BALB/c mice were sensitized and challenged with HDM. Bronchoalveolar lavage fluid (BALF), airway inflammation and hyperresponsiveness (AHR), serum immunoglobulin and splenic T cells were assessed. Age-related T cell activation was analyzed in a co-culture with bone marrow-derived dendritic cells (BMDC) and splenic CD4(+)T cells from young and old mice.ResultsFeatures of allergic airway disease such as mucous cell hyperplasia, infiltration of airway eosinophils and lymphocytes, Th2 cytokine expression and serum IgG1 levels were greater in old compared to young mice. In contrast to the more marked inflammatory/immune responses to HDM in old mice, AHR was greater in young HDM-treated mice. Only the old mice developed airway neutrophil infiltration and a Th17 immune response upon HDM exposure, with increases in BALF cytokines IL-17A and KC, and Th17 cytokine producing T cells in the spleen. Stimulation of CD4(+)T cells and BMDC co-cultures with HDM, resulted in an enhanced Th17 cytokine response in cells isolated from old mice.Conclusions and Clinical RelevanceOur findings in mice suggest that the severity and character of allergic airway disease are age dependent, with a bias towards a Th17 immune response with aging. Elderly, asthmatics may be prone to develop severe allergic airway inflammation with a mixed Th2/Th17 immune response.