IL-13 is key mediator of allergic inflammation in asthmatic patients. We have previously shown that the decoy receptor IL-13 receptor (IL-13R) ⍺2 attenuates responses of fibroblasts to IL-13. Because the expression of IL-13R⍺2 can be regulated by IFN-γ, a type II interferon, we hypothesized that innate antiviral responses characterized by type I interferon expression can also induce IL-13R⍺2 expression.

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⍺2.

Primary human fibroblasts were cultured from endobronchial biopsy specimens obtained from healthy or asthmatic volunteers and challenged with dsRNA. Upregulation of IL-13R⍺2 mRNA was measured by using real-time quantitative PCR, and cell-surface IL-13R⍺2 protein expression was measured by using fluorescence-activated cell sorting. Eotaxin release was determined by means of ELISA.

Direct treatment with IFN-β led to an upregulation of IL-13R⍺2. Exposure to dsRNA rapidly induced IFN-β mRNA in fibroblasts, and this was followed by significant induction of IL-13R⍺2 mRNA and cell-surface protein expression, which was dependent on de novo protein synthesis. A neutralizing antibody to the IFN-⍺/β receptor blocked cell-surface expression of IL-13R⍺2 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⍺2 neutralizing antibody restored IL-13–stimulated eotaxin production in dsRNA-treated cells.

IFN-β induces IL-13R⍺2 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⍺2 in human bronchial fibroblasts during viral infection.