TSLP促进肌成纤维细胞向哮喘小鼠气道募集

TSLP promotes recruitment of myofibroblasts into airway in asthmatic mice

目的:探讨胸腺基质淋巴细胞生成素(Thymic stromal lymphopoietin,TSLP)与慢性哮喘小鼠气道组织中浸润的肌成纤维细胞的关系。方法:将12只BALB/c小鼠随机分为4组:生理盐水组、屋尘螨(House dust mite,HDM)组、anti-TSLP组、同型对照组。激光共聚焦检测气道组织中出现的肌成纤维细胞。ELISA法检测肺泡灌洗液中TSLP、TGF-β1、IL-25和IL-33的表达水平。结果:拮抗TSLP可显著抑制HDM持续暴露导致的气道结构改变,减少肌成纤维细胞向哮喘小鼠气道组织募集。Anti-TSLP组小鼠BALF中TSLP、TGF-β1和IL-33蛋白水平也较同型对照组明显降低(P值均<0.05)。结论:TSLP促进肌成纤维细胞向慢性哮喘小鼠气道募集是其参与气道重塑的主要机制之一。

Objective：To investigate whether thymic stromal lymphopoietin （ TSLP） participate in asthmatic airway remodeling partially by promoting myofibroblast accumulating in the lung. Methods：Twelve mice evenly were randomly divided into four groups：a saline group;an HDM-exposed group;an IgG isotype-treated group and an anti-TSLP-treated group. The supernatant of bronchoalveolar lavage fluid （ BALF） was used to analyze the levels of TSLP,IL-25 and IL-33 by ELISA. Fluorescence-labeled collagenⅠ（ ColⅠ）/α-smooth muscle actin （α-SMA） -dual-positive myofibroblasts were examined by confocal microscopy. Results：Chronic allergen exposure induced obviously abnormal airway structural changes,which were inhibited by blocking TSLP. We detected a highly increased number of myofibroblasts in the sub-epithelial zone in mice from HDM-challenged group. However, TSLP neutralization significantly reduced myofibroblasts recruitment. Moreover,blocking TSLP not only decreased the level of TSLP,but also inhibited the expression levels of TGF-β1 and IL-33 in BAL fluid. Conclusion：The results suggest that orchestrating myofibroblasts recruiting into the lungs is one of the main pathogenesis that TSLP involves in airway remodeling in asthmatic mice.