Thymic stromal lymphopoietin contribution to the recruitment of circulating fibrocytes to the lung in a mouse model of chronic allergic asthma.

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-ß1 in the bronchoalveolar lavage (BAL) fluid was determined by ELISA. Results: We found significantly increased levels of TSLP and TGF-ß1 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-ß1, 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.