嗜酸性粒细胞在气道壁中的分布对于哮喘气道高反应性和T2炎症的特定特征至关重要
2022/01/28
摘要
嗜酸性粒细胞是哮喘中的效应细胞，但嗜酸性粒细胞在气道壁中精确定位的功能意义尚不清楚。我们的目的是量化气道壁不同隔室中的嗜酸性粒细胞，并将这些发现与哮喘的临床特征和气道炎症标志物进行相关分析。在这项横断面研究中，我们利用基于设计的体视学精确划分哮喘患者和非哮喘患者的上皮室和上皮下间隙（包括粘膜下层在内的基膜下气道壁区域）中嗜酸性粒细胞的数量密度，并将这些发现与气道高反应性（AHR）和呼吸道炎症特征进行关联分析。上皮内嗜酸性粒细胞与哮喘和内源性AHR的存在有关，而内源性AHR是哮喘最特异的表现之一。相反，上皮内和上皮下嗜酸性粒细胞均与2型（T2）炎症相关，IL5表达与上皮内嗜酸性粒细胞之间的相关性最强。气道壁嗜酸性粒细胞浸润与哮喘中描述的特定肥大细胞表型有关。我们发现IL-33和IL-5增加了嗜酸性粒细胞产生的半胱氨酸白三烯（CysLT），CysLT LTC4和IL-33增加了肥大细胞中IL-13的表达，并改变了它们的蛋白酶谱。我们得出结论，上皮内嗜酸性粒细胞与内源性AHR和T2炎症有关，并可能通过细胞周期性淋巴细胞与上皮内肥大细胞相互作用来调节气道炎症。
Location of eosinophils in the airway wall is critical for specific features of airway hyperresponsiveness and T2 inflammation in asthma
Taha Al-Shaikhly, Ryan C Murphy, Andrew Parker, Ying Lai, Matthew C Altman, Megan Larmore, William A Altemeier, Charles W Frevert, Jason S Debley, Adrian M Piliponsky, Steven F Ziegler, Michael C Peters, Teal S Hallstrand
Abstract
Eosinophils are implicated as effector cells in asthma but the functional implications of the precise location of eosinophils in the airway wall is poorly understood. We aimed to quantify eosinophils in the different compartments of the airway wall and associate these findings with clinical features of asthma and markers of airway inflammation. In this cross-sectional study, we utilised design-based stereology to accurately partition the numerical density of eosinophils in both the epithelial compartment and the subepithelial space (airway wall area below the basal lamina including the submucosa) in individuals with and without asthma and related these findings to airway hyperresponsiveness (AHR) and features of airway inflammation. Intraepithelial eosinophils were linked to the presence of asthma and endogenous AHR, the type of AHR that is most specific for asthma. In contrast, both intraepithelial and subepithelial eosinophils were associated with type-2 (T2) inflammation, with the strongest association between IL5 expression and intraepithelial eosinophils. Eosinophil infiltration of the airway wall was linked to a specific mast cell phenotype that has been described in asthma. We found that IL-33 and IL-5 additively increased cysteinyl leukotriene (CysLT) production by eosinophils and that the CysLT LTC4 along with IL-33 increased IL13 expression in mast cells and altered their protease profile. We conclude that intraepithelial eosinophils are associated with endogenous AHR and T2 inflammation and may interact with intraepithelial mast cells via CysLTs to regulate airway inflammation.
嗜酸性粒细胞是哮喘中的效应细胞，但嗜酸性粒细胞在气道壁中精确定位的功能意义尚不清楚。我们的目的是量化气道壁不同隔室中的嗜酸性粒细胞，并将这些发现与哮喘的临床特征和气道炎症标志物进行相关分析。在这项横断面研究中，我们利用基于设计的体视学精确划分哮喘患者和非哮喘患者的上皮室和上皮下间隙（包括粘膜下层在内的基膜下气道壁区域）中嗜酸性粒细胞的数量密度，并将这些发现与气道高反应性（AHR）和呼吸道炎症特征进行关联分析。上皮内嗜酸性粒细胞与哮喘和内源性AHR的存在有关，而内源性AHR是哮喘最特异的表现之一。相反，上皮内和上皮下嗜酸性粒细胞均与2型（T2）炎症相关，IL5表达与上皮内嗜酸性粒细胞之间的相关性最强。气道壁嗜酸性粒细胞浸润与哮喘中描述的特定肥大细胞表型有关。我们发现IL-33和IL-5增加了嗜酸性粒细胞产生的半胱氨酸白三烯（CysLT），CysLT LTC4和IL-33增加了肥大细胞中IL-13的表达，并改变了它们的蛋白酶谱。我们得出结论，上皮内嗜酸性粒细胞与内源性AHR和T2炎症有关，并可能通过细胞周期性淋巴细胞与上皮内肥大细胞相互作用来调节气道炎症。
(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校)
(Eur Respir J.2022 Jan 13;2101865. doi: 10.1183/13993003.01865-2021.)
(Eur Respir J.2022 Jan 13;2101865. doi: 10.1183/13993003.01865-2021.)
Location of eosinophils in the airway wall is critical for specific features of airway hyperresponsiveness and T2 inflammation in asthma
Taha Al-Shaikhly, Ryan C Murphy, Andrew Parker, Ying Lai, Matthew C Altman, Megan Larmore, William A Altemeier, Charles W Frevert, Jason S Debley, Adrian M Piliponsky, Steven F Ziegler, Michael C Peters, Teal S Hallstrand
Abstract
Eosinophils are implicated as effector cells in asthma but the functional implications of the precise location of eosinophils in the airway wall is poorly understood. We aimed to quantify eosinophils in the different compartments of the airway wall and associate these findings with clinical features of asthma and markers of airway inflammation. In this cross-sectional study, we utilised design-based stereology to accurately partition the numerical density of eosinophils in both the epithelial compartment and the subepithelial space (airway wall area below the basal lamina including the submucosa) in individuals with and without asthma and related these findings to airway hyperresponsiveness (AHR) and features of airway inflammation. Intraepithelial eosinophils were linked to the presence of asthma and endogenous AHR, the type of AHR that is most specific for asthma. In contrast, both intraepithelial and subepithelial eosinophils were associated with type-2 (T2) inflammation, with the strongest association between IL5 expression and intraepithelial eosinophils. Eosinophil infiltration of the airway wall was linked to a specific mast cell phenotype that has been described in asthma. We found that IL-33 and IL-5 additively increased cysteinyl leukotriene (CysLT) production by eosinophils and that the CysLT LTC4 along with IL-33 increased IL13 expression in mast cells and altered their protease profile. We conclude that intraepithelial eosinophils are associated with endogenous AHR and T2 inflammation and may interact with intraepithelial mast cells via CysLTs to regulate airway inflammation.
上一篇：
雄激素受体信号在过敏性气道炎症中促进Treg抑制功能
下一篇：
剖宫产新生儿代谢与儿童哮喘风险
