Distinct Tlr4-expressing cell compartments control neutrophilic and eosinophilic airway inflammation.
Distinct Tlr4-expressing cell compartments control neutrophilic and eosinophilic airway inflammation.
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作者：
过敏性哮喘是一种慢性炎症性肺部疾病。一些形式的过敏性哮喘的特征在于Th 2驱动的嗜酸性粒细胞增多，而其他形式的过敏性哮喘的特征在于Th 17驱动的嗜酸性粒细胞增多。Toll样受体4（TLR 4）对造血细胞和气道上皮细胞（AEC）的刺激有助于对脂多糖（LPS）和过敏原的炎症反应，但TLR 4在这些细胞区室中对气道炎症反应的具体贡献仍然知之甚少。我们使用新的条件突变Tlr 4fl/fl小鼠来确定AEC和造血细胞Tlr 4表达对LPS和变应原诱导的气道炎症的相对贡献。我们发现造血细胞表达Tlr 4对于LPS暴露后的嗜肺性气道炎症和Th 17驱动的对屋尘螨（HDM）裂解物和卵清蛋白（OVA）的嗜肺性应答是至关重要的。相反，发现AEC的Tlr 4表达对于用这些相同的变应原致敏和激发后的强嗜酸性气道炎症是重要的。因此，造血和气道上皮细胞的Tlr 4表达控制对吸入过敏原的免疫应答的不同分支。
Allergic asthma is a chronic, inflammatory lung disease. Some forms of allergic asthma are characterized by Th2-driven eosinophilia while others are distinguished by Th17-driven neutrophilia. Stimulation of Toll-like receptor 4 (TLR4) on hematopoietic and airway epithelial cells (AECs) contributes to the inflammatory response to lipopolysaccharide (LPS) and allergens, but the specific contribution of TLR4 in these cell compartments to airway inflammatory responses remains poorly understood. We used novel, conditionally mutant Tlr4fl/fl mice to define the relative contributions of AEC and hematopoietic cell Tlr4 expression to LPS- and allergen-induced airway inflammation. We found that Tlr4 expression by hematopoietic cells is critical for neutrophilic airway inflammation following LPS exposure and for Th17-driven neutrophilic responses to the house dust mite (HDM) lysates and ovalbumin (OVA). Conversely, Tlr4 expression by AECs was found to be important for robust eosinophilic airway inflammation following sensitization and challenge with these same allergens. Thus, Tlr4 expression by hematopoietic and airway epithelial cells controls distinct arms of the immune response to inhaled allergens.
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影响因子：
4.3
作者：
Barczyk, A;Pierzchala, W;Sozañska, E
通讯作者：
Sozañska, E
影响因子：
4.4
作者：
Kurowska-Stolarska, Mariola;Kewin, Pete;Xu, Damo
通讯作者：
Xu, Damo
影响因子：
10
作者：
Green, RH;Brightling, CE;Pavord, ID
通讯作者：
Pavord, ID
DOI：
10.1164/rccm.200407-953oc
发表时间：
2005-04-15
影响因子：
24.7
作者：
Hollingsworth, JW;Chen, BJ;Schwartz, DA
通讯作者：
Schwartz, DA
DOI：
10.1073/pnas.0510839103
发表时间：
2006-02-14
影响因子：
11.1
作者：
Harris, KS;Zhang, Z;Sun, X
通讯作者：
Sun, X