慢性过敏性气道炎症中Th17反应阻碍了调节性T细胞介导的免疫耐受及其促气道重塑作用
2012/10/11
摘要
Th17型反应在哮喘患者气道重塑中的作用尚不清楚。我们研究显示，胃肠外和粘膜过敏原致敏，随后过敏原吸入，可导致Th17型肺免疫反应。与体外产生的Th17细胞不同的是，肺内Th17细胞不能产生肿瘤坏死因子-α和IL-22。嗜酸性粒细胞增多主要见于急性炎症，中性粒细胞增多和IL-17增多主要见于慢性疾病。过敏原诱导的耐受与Foxp3-、Helios-和主要表达糖蛋白-A重复序列的调节性T细胞（Treg）及IL-10/干扰素-γ相关。致敏的肺内存在Treg表现型改变，而吸入IL-17能消除该Treg表现型。在对gp130遗传紊乱的Th17缺陷小鼠研究中，结果显示Th17细胞诱导气道重构，该作用与Th2反应无关。给予全反式视黄酸能缓解Th17介导的疾病，增加Treg活性，而给予地塞米松能抑制嗜酸性粒细胞增多，但对中性粒细胞增多无影响，同时会增加体外Th17的发育。针对Th17/Treg轴，可能对中性粒细胞性和糖皮质激素难治性哮喘具有一定治疗作用。
（刘国梁 审校）
Mucosal Immunol. 2012 Aug 15. doi: 10.1038/mi.2012.76. [Epub ahead of print]
Th17 responses in chronic allergic airway inflammation abrogate regulatory T-cell-mediated tolerance and contribute to airway remodeling.
Zhao J, Lloyd CM, Noble A.
Source
Department of Asthma Allergy and Respiratory Science, MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, King’s College London, London, UK.
Abstract
The role of T-helper type 17 (Th17) responses in airway remodeling in asthma is currently unknown. We demonstrate that both parenteral and mucosal allergen sensitization, followed by allergen inhalation, leads to Th17-biased lung immune responses. Unlike Th17 cells generated in vitro, lung Th17 cells did not produce tumor necrosis factor-α or interleukin (IL)-22. Eosinophilia predominated in acute inflammation, while neutrophilia and IL-17 increased in chronic disease. Allergen-induced tolerance involved Foxp3-, Helios-, and glycoprotein-A repetitions predominant-expressing regulatory T cells (Treg) and IL-10/interferon-γ priming. This Treg phenotype was altered in inflamed lungs and abrogated by inhalation of IL-17. Using Th17-deficient mice with genetic disruption of gp130 in T cells, we showed that Th17 cells induce airway remodeling independent of the Th2 response. All-trans retinoic acid administration ameliorated Th17-mediated disease and increased Treg activity, while dexamethasone inhibited eosinophilia but not neutrophilia, and enhanced Th17 development in vitro. Targeting the Th17/Treg axis might therefore be therapeutic in neutrophilic and glucocorticoid-refractory asthma.
Mucosal Immunol. 2012 Aug 15. doi: 10.1038/mi.2012.76. [Epub ahead of print]
Th17型反应在哮喘患者气道重塑中的作用尚不清楚。我们研究显示，胃肠外和粘膜过敏原致敏，随后过敏原吸入，可导致Th17型肺免疫反应。与体外产生的Th17细胞不同的是，肺内Th17细胞不能产生肿瘤坏死因子-α和IL-22。嗜酸性粒细胞增多主要见于急性炎症，中性粒细胞增多和IL-17增多主要见于慢性疾病。过敏原诱导的耐受与Foxp3-、Helios-和主要表达糖蛋白-A重复序列的调节性T细胞（Treg）及IL-10/干扰素-γ相关。致敏的肺内存在Treg表现型改变，而吸入IL-17能消除该Treg表现型。在对gp130遗传紊乱的Th17缺陷小鼠研究中，结果显示Th17细胞诱导气道重构，该作用与Th2反应无关。给予全反式视黄酸能缓解Th17介导的疾病，增加Treg活性，而给予地塞米松能抑制嗜酸性粒细胞增多，但对中性粒细胞增多无影响，同时会增加体外Th17的发育。针对Th17/Treg轴，可能对中性粒细胞性和糖皮质激素难治性哮喘具有一定治疗作用。
（刘国梁 审校）
Mucosal Immunol. 2012 Aug 15. doi: 10.1038/mi.2012.76. [Epub ahead of print]
Th17 responses in chronic allergic airway inflammation abrogate regulatory T-cell-mediated tolerance and contribute to airway remodeling.
Zhao J, Lloyd CM, Noble A.
Source
Department of Asthma Allergy and Respiratory Science, MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, King’s College London, London, UK.
Abstract
The role of T-helper type 17 (Th17) responses in airway remodeling in asthma is currently unknown. We demonstrate that both parenteral and mucosal allergen sensitization, followed by allergen inhalation, leads to Th17-biased lung immune responses. Unlike Th17 cells generated in vitro, lung Th17 cells did not produce tumor necrosis factor-α or interleukin (IL)-22. Eosinophilia predominated in acute inflammation, while neutrophilia and IL-17 increased in chronic disease. Allergen-induced tolerance involved Foxp3-, Helios-, and glycoprotein-A repetitions predominant-expressing regulatory T cells (Treg) and IL-10/interferon-γ priming. This Treg phenotype was altered in inflamed lungs and abrogated by inhalation of IL-17. Using Th17-deficient mice with genetic disruption of gp130 in T cells, we showed that Th17 cells induce airway remodeling independent of the Th2 response. All-trans retinoic acid administration ameliorated Th17-mediated disease and increased Treg activity, while dexamethasone inhibited eosinophilia but not neutrophilia, and enhanced Th17 development in vitro. Targeting the Th17/Treg axis might therefore be therapeutic in neutrophilic and glucocorticoid-refractory asthma.
Mucosal Immunol. 2012 Aug 15. doi: 10.1038/mi.2012.76. [Epub ahead of print]
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农场效应，或者农场环境对哮喘和过敏性疾病的保护作用
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冬季气温下降和二氧化硫水平影响韩国难治性哮喘发作：对顺天乡哮喘队列数据的时间-趋势、对照、病例-交叉
