IgE-dependent TSLP production by human mast cells and the role of mast cell-derived TSLP in bronchial asthma

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To investigate the thymic stromal lymphopoietin (TSLP) expression in asthmatic bronchial mucosa, we determined the cell populations expressing TSLP in the lungs of 16 asthmatics and of 11 controls by using immunohistochemistry. Ninety % of TSLP^+ cells were mast cells in the airways and the number of TSLP^+ mast cells was significantly increased in the airways of asthmatics (P < 0.0001). There was a significant correlation between the number of TSLP^+ mast cells and serum IgE level, hyperresponsibility, eosinophil count in the blood and the sputum, suggesting that mast cell-derived TSLP may play an important role in the pathogenesis of asthma. FcεRI-mediated activation of human mast cells upregulated TSLP mRNA expression 5.2±2.9 fold, and IL-4 significantly enhanced the FcεRI-mediated expression (53.7±15.9 fold, P< 0.05), but LPS and polyI : C failed to induce TSLP mRNA. We confirmed the production of TSLP in MC pellets and mast cell supernatants after activation in the presence of protease inhibitors, indicating mast cells are one of the main sources of TSLP in bronchial asthma.