Location of eosinophils in the airway wall is critical for specific features of airway hyperresponsiveness and T2 inflammation in asthma.
Location of eosinophils in the airway wall is critical for specific features of airway hyperresponsiveness and T2 inflammation in asthma.
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DOI：
10.1183/13993003.01865-2021
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发表时间：
2022-08
期刊：
影响因子：
--
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中科院分区：
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--
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嗜酸性粒细胞在哮喘中被认为是效应细胞，但嗜酸性粒细胞在气道壁的精确定位的功能意义知之甚少。我们的目的是量化嗜酸性粒细胞在气道壁的不同部分，并将这些发现与哮喘的临床特征和气道炎症的标志物。在这项横断面研究中，我们利用设计为基础的体视学，准确地分区嗜酸性粒细胞的数量密度在上皮室和上皮下空间（气道壁面积低于基底层，包括粘膜下层）在个人与哮喘和相关的这些发现气道高反应性（AHR）和气道炎症的特点。上皮内嗜酸性粒细胞与哮喘和内源性AHR的存在有关，AHR是哮喘最特异的类型。相比之下，上皮内和上皮下嗜酸性粒细胞与2型（T2）炎症，IL 5的表达和上皮内嗜酸性粒细胞之间的最强关联。嗜酸性粒细胞浸润的气道壁与一个特定的肥大细胞表型，已被描述在哮喘。我们发现白细胞介素（IL）-33和IL-5可相加地增加嗜酸性粒细胞产生的半胱氨酸白三烯（CysLT），并且CysLT LTC 4沿着IL-33增加肥大细胞中IL 13的表达并改变其蛋白酶谱。我们的结论是，上皮内嗜酸性粒细胞与内源性AHR和T2炎症，并可能通过CysLTs与上皮内肥大细胞相互作用，以调节气道炎症。上皮内嗜酸性粒细胞是哮喘的特异性特征，与内源性气道高反应性和2型炎症相关，并可通过半胱氨酰白三烯与上皮内肥大细胞相互作用以调节气道炎症。https://bit.ly/3e1QFo1
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 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 interleukin (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. Intraepithelial eosinophils are a specific feature of asthma, associated with endogenous airway hyperresponsiveness and type 2 inflammation, and may interact with intraepithelial mast cells via cysteinyl leukotrienes to regulate airway inflammation https://bit.ly/3e1QFo1
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影响因子：
17.1
作者：
Drake MG;Scott GD;Blum ED;Lebold KM;Nie Z;Lee JJ;Fryer AD;Costello RW;Jacoby DB
通讯作者：
Jacoby DB
影响因子：
14.2
作者：
Dougherty, Ryan H.;Sidhu, Sukhvinder S.;Raman, Kavita;Solon, Margaret;Solberg, Owen D.;Caughey, George H.;Woodruff, Prescott G.;Fahy, John V.
通讯作者：
Fahy, John V.
DOI：
10.1164/rccm.201301-0084oc
发表时间：
2013-07-01
影响因子：
24.7
作者：
Hallstrand, Teal S.;Lai, Ying;Gelb, Michael H.
通讯作者：
Gelb, Michael H.
DOI：
10.1056/nejmoa0808991
发表时间：
2009-03-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Haldar P;Brightling CE;Hargadon B;Gupta S;Monteiro W;Sousa A;Marshall RP;Bradding P;Green RH;Wardlaw AJ;Pavord ID
通讯作者：
Pavord ID
影响因子：
9.6
作者：
Duong, MyLinh;Subbarao, Padmaja;O'Byrne, Paid M.
通讯作者：
O'Byrne, Paid M.