Chen Zhuang-Gui, Meng Ping, Li Hong-Tao, Li Ming, Yang Li-Fen, Yan Yan, Li Ya-Ting, Zou Xiao-Ling, Wang De-Yun, Zhang Tian-Tuo
a Department of Pulmonary Diseases, The Third Affiliated Hospital of Sun Yat-Sen University , Institute of Respiratory Diseases of Sun Yat-Sen University , Guangzhou , China.
b Department of Pediatrics , The Third Affiliated Hospital of Sun Yat-Sen University , Guangzhou , China.
J Asthma. 2018 Sep;55(9):975-983. doi: 10.1080/02770903.2017.1386213. Epub 2017 Oct 30.
: Fibrocyte localization to the airways and thymic stromal lymphopoietin (TSLP) overexpression in the lung are features of severe asthma. The aim of this study was to determine whether TSLP contributes to fibrocyte trafficking and airway remodeling in a mouse model of allergic asthma. : We established a chronic asthma animal model by administering house dust mite (HDM) extracts intranasally for up to 5 consecutive weeks. Mouse anti-TSLP monoclonal antibody (mAb) was given intraperitoneally starting the 4 week. Fluorescence-labeled CD34/collagen I (Col I)-dual-positive fibrocytes were examined by confocal microscopy. The level of TGF-β1 in the bronchoalveolar lavage (BAL) fluid was determined by ELISA. : We found significantly increased levels of TSLP and TGF-β1 in the lung of the mice subjected to repeated allergen exposure, which was accompanied by increased number of fibrocytes in the sub-epithelial zone and the BAL fluid. However, blocking TSLP markedly decreased the production of TGF-β1, reduced the number of fibrocytes and subsequently prevented alterations of both airway and vascular structures. : Our data suggested that TSLP might function in airway remodeling by promoting circulating fibrocyte recruitment to the lung in the mice subjected to chronic allergen exposure. These results provide a better rationale for targeting the interaction between TSLP and fibrocytes as a therapeutic approach for chronic allergic asthma.
成纤维细胞定位于气道以及肺中胸腺基质淋巴细胞生成素(TSLP)的过表达是重度哮喘的特征。本研究的目的是确定TSLP是否在过敏性哮喘小鼠模型中促成纤维细胞的迁移和气道重塑。
我们通过鼻内给予屋尘螨(HDM)提取物连续5周建立了慢性哮喘动物模型。从第4周开始腹腔注射小鼠抗TSLP单克隆抗体(mAb)。通过共聚焦显微镜检查荧光标记的CD34/胶原蛋白I(Col I)双阳性成纤维细胞。通过ELISA测定支气管肺泡灌洗(BAL)液中TGF-β1的水平。
我们发现,反复接触过敏原的小鼠肺中TSLP和TGF-β1水平显著升高,同时上皮下区域和成纤维细胞数量增加。然而,阻断TSLP可显著降低TGF-β1的产生,减少成纤维细胞数量,并随后防止气道和血管结构的改变。
我们的数据表明,在慢性过敏原暴露的小鼠中,TSLP可能通过促进循环成纤维细胞募集到肺中而在气道重塑中发挥作用。这些结果为将TSLP与成纤维细胞之间的相互作用作为慢性过敏性哮喘的治疗方法提供了更好的理论依据。
J Allergy Clin Immunol. 2013-6-26