Airway epithelial cells activate T_H2 cytokine production in mast cells through IL-1 and thymic stromal lymphopoietin

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• 作者：Deepti R. Nagarkar ; Julie A. Poposki ; Michael R. Comeau ; Assel Biyasheva ; Pedro C. Avila ; Robert P. Schleimer ; Atsushi Kato
• 关键词：Epithelial cells ; mast cells ; virus ; asthma ; TH2 cytokine ; IL-1 ; thymic stromal lymphopoietin
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2012
• 出版时间：July, 2012
• 年：2012
• 卷：130
• 期：1
• 页码：225-232.e4
• 全文大小：709 K

文摘

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ass=""h4"">Background

Airway epithelial cells are important regulators of innate and adaptive immunity. Although mast cells are known to play a central role in manifestations of allergic inflammation and are found in the epithelium in patients with T_H2-related diseases, their role is incompletely understood.

ass=""h4"">Objectives

The objective of this study was to investigate the role of airway epithelial cells in the production of T_H2 cytokines in mast cells.

ass=""h4"">Methods

Normal human bronchial epithelial (NHBE) cells were stimulated with TNF, IL-4, IFN-¦Ã, IL-17A, and double-stranded RNA (dsRNA) alone or in combination. Human mast cells were stimulated with epithelial cell-derived supernatants or cocultured with NHBE cells. T_H2 cytokine responses were blocked with neutralizing antibodies.

ass=""h4"">Results

Supernatants from IL-4- and dsRNA-stimulated NHBE cells significantly enhanced T_H2 cytokine production from mast cells. The combination of IL-4 and dsRNA itself or supernatants from NHBE cells stimulated with other cytokines did not activate mast cells, suggesting that mast cell responses were induced by epithelial cell factors that were only induced by IL-4 and dsRNA. Epithelial supernatant-dependent T_H2 cytokine production in mast cells was suppressed by anti-IL-1 and anti- thymic stromal lymphopoietin (TSLP) and was enhanced by anti-IL-1 receptor antagonist. Similar results were observed in coculture experiments. Finally, we found dsRNA-dependent production of IL-1, TSLP, and IL-1 receptor antagonist in NHBE cells was regulated by T_H cytokines, and their ratio in NHBE cells correlated with T_H2 cytokine production in mast cells.

ass=""h4"">Conclusions

Pathogens producing dsRNA, such as respiratory viral infections, might amplify local T_H2 inflammation in asthmatic patients through the production of TSLP and IL-1 by epithelial cells and subsequent activation of T_H2 cytokine production by mast cells in the airways.