Zhuang-Gui Chen1,2, Ping Meng1, Hong-Tao Li1, Ming Li3, Li-Fen Yang2, Yan Yan4, Ya-Ting Li2, Xiao-Ling Zou1, De-Yun Wang4, Tian-Tuo Zhang1. 1. 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. 2. b Department of Pediatrics , The Third Affiliated Hospital of Sun Yat-Sen University , Guangzhou , China. 3. c Department of Pulmonary Diseases, The First Affiliated Hospital of Sun Yat-Sen University , Institute of Respiratory Diseases of Sun Yat-Sen University , Guangzhou , China. 4. d Department of Otolaryngology, Yong Loo Lin School of Medicine , National University of Singapore , Singapore.
Abstract
Objective: 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. Methods: 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 4th 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. Results: 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. Conclusions: 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.
Objective: 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. Methods: 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 4th 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. Results: 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. Conclusions: 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.
Authors: Laura Polányi; Carien M Niessen; Christina Vohlen; Julia Stinn; Tobias Kretschmer; Vanessa Jentgen; Dharmesh Hirani; Silke V Koningsbruggen-Rietschel; Jörg Dötsch; Miguel A Alejandre Alcazar Journal: J Mol Med (Berl) Date: 2020-01-07 Impact factor: 4.599