The innate antiviral response upregulates IL-13 receptor ¦Á2 in bronchial fibroblasts

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• 作者：Gemma Campbell-Harding ; PhD ; Hannah Sawkins ; BSc ; Nicole Bedke ; PhD ; Stephen T. Holgate ; DM ; Donna E. Davies ; PhD ; Allison-Lynn Andrews ; PhD ; ^{ala@soton.ac.uk}
• 关键词：Virus ; cytokine receptors ; fibroblasts ; type I interferon
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2013
• 出版时间：March, 2013
• 年：2013
• 卷：131
• 期：3
• 页码：849-855.e5
• 全文大小：677 K

文摘

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Background

IL-13 is key mediator of allergic inflammation in asthmatic patients. We have previously shown that the decoy receptor IL-13 receptor (IL-13R) ¦Á2 attenuates responses of fibroblasts to IL-13. Because the expression of IL-13R¦Á2 can be regulated by IFN-¦Ã, a type II interferon, we hypothesized that innate antiviral responses characterized by type I interferon expression can also induce IL-13R¦Á2 expression.

Objective

We sought to induce an innate antiviral response in?primary fibroblasts using exposure to double-stranded RNA?(dsRNA) and to examine the expression and function of IL-13R¦Á2.

Methods

Primary human fibroblasts were cultured from endobronchial biopsy specimens obtained from healthy or asthmatic volunteers and challenged with dsRNA. Upregulation of IL-13R¦Á2 mRNA was measured by using real-time quantitative PCR, and cell-surface IL-13R¦Á2 protein expression was measured by using fluorescence-activated cell sorting. Eotaxin release was determined by means of ELISA.

Results

Direct treatment with IFN-¦Â led to an upregulation of IL-13R¦Á2. Exposure to dsRNA rapidly induced IFN-¦Â mRNA in fibroblasts, and this was followed by significant induction of IL-13R¦Á2 mRNA and cell-surface protein expression, which was dependent on de novo protein synthesis. A?neutralizing antibody to the IFN-¦Á/¦Â receptor blocked cell-surface expression of IL-13R¦Á2 in the presence of dsRNA. Pretreatment of fibroblasts with dsRNA led to attenuation of IL-13-stimulated eotaxin production. However, the presence of an IL-13R¦Á2 neutralizing antibody restored IL-13-stimulated eotaxin production in dsRNA-treated cells.

Conclusion

IFN-¦Â induces IL-13R¦Á2 expression, leading to a consequential suppression of responsiveness to IL-13. These data suggest cross-talk between T_H1 and T_H2 pathways and point to an immunomodulatory role for IL-13R¦Á2 in human bronchial fibroblasts during viral infection.