Davinder Kaur1, Camille Doe1, Lucy Woodman1, Wing-Yan Heidi Wan1, Amanda Sutcliffe1, Fay Hollins1, Christopher Brightling2. 1. Institute for Lung Health, Department of Infection, Inflammation and Immunity, University of Leicester, Leicester, England. 2. Institute for Lung Health, Department of Infection, Inflammation and Immunity, University of Leicester, Leicester, England. Electronic address: ceb17@le.ac.uk.
Abstract
BACKGROUND: The mast cell localization to airway smooth muscle (ASM) bundle in asthma is important in the development of disordered airway physiology. Thymic stromal lymphopoietin (TSLP) is expressed by airway structural cells. Whether it has a role in the crosstalk between these cells is uncertain. We sought to define TSLP expression in bronchial tissue across the spectrum of asthma severity and to investigate the TSLP and TSLP receptor (TSLPR) expression and function by primary ASM and mast cells alone and in coculture. METHODS: TSLP expression was assessed in bronchial tissue from 18 subjects with mild to moderate asthma, 12 with severe disease, and nine healthy control subjects. TSLP and TSLPR expression in primary mast cells and ASM was assessed by immunofluorescence, flow cytometry, and enzyme-linked immunosorbent assay, and its function was assessed by calcium imaging. The role of TSLP in mast cell and ASM proliferation, survival, differentiation, synthetic function, and contraction was examined. RESULTS: TSLP expression was increased in the ASM bundle in mild-moderate disease. TSLP and TSLPR were expressed by mast cells and ASM and were functional. Mast cell activation by TSLP increased the production of a broad range of chemokines and cytokines, but did not affect mast cell or ASM proliferation, survival, or contraction. CONCLUSIONS: TSLP expression by the bronchial epithelium and ASM was upregulated in asthma. TSLP promoted mast cell synthetic function, but did not contribute to other functional consequences of mast cell-ASM crosstalk.
BACKGROUND: The mast cell localization to airway smooth muscle (ASM) bundle in asthma is important in the development of disordered airway physiology. Thymic stromal lymphopoietin (TSLP) is expressed by airway structural cells. Whether it has a role in the crosstalk between these cells is uncertain. We sought to define TSLP expression in bronchial tissue across the spectrum of asthma severity and to investigate the TSLP and TSLP receptor (TSLPR) expression and function by primary ASM and mast cells alone and in coculture. METHODS: TSLP expression was assessed in bronchial tissue from 18 subjects with mild to moderate asthma, 12 with severe disease, and nine healthy control subjects. TSLP and TSLPR expression in primary mast cells and ASM was assessed by immunofluorescence, flow cytometry, and enzyme-linked immunosorbent assay, and its function was assessed by calcium imaging. The role of TSLP in mast cell and ASM proliferation, survival, differentiation, synthetic function, and contraction was examined. RESULTS: TSLP expression was increased in the ASM bundle in mild-moderate disease. TSLP and TSLPR were expressed by mast cells and ASM and were functional. Mast cell activation by TSLP increased the production of a broad range of chemokines and cytokines, but did not affect mast cell or ASM proliferation, survival, or contraction. CONCLUSIONS: TSLP expression by the bronchial epithelium and ASM was upregulated in asthma. TSLP promoted mast cell synthetic function, but did not contribute to other functional consequences of mast cell-ASM crosstalk.
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