Upregulation of B7 molecules (CD80 and CD86) and exacerbated eosinophilic pulmonary inflammatory response in mice lacking the IFN-β gene

Abstract

Background: IFN-β has been shown to be effective as therapy for multiple sclerosis. Some reports attributed its beneficial effects to the capacity to induce a TH2 response. However, other studies have suggested that endogenous type I IFN might downregulate the allergic response in mice. Objective: We sought to define the differential role of endogenous IFN-β in controlling the development of allergic inflammation. Methods: We assessed whether deletion of the gene encoding IFN-β (IFNB) with knockout mice participated in the development of allergic response in ovalbumin (OVA)-sensitized and OVA-challenged mice. Results: OVA-sensitized and OVA-challenged mice with lack of the IFNB gene had more severe pulmonary inflammation with increased lung local response, including IL-4, IL-5, IL-13, IgE, eosinophilia, and goblet cells, than their litter mates (IFN-β+/-), whereas no differences were observed in regard to local levels of IFN-γ. Moreover, systemic response with IgE production is also enhanced. Lack of IFN-β also results in significantly higher antigen-specific T cells, with higher levels of IL-4, IL-5, and IL-13, whereas no significant differences in IFN-γ response could be observed. We have also detected a higher ratio of CD4+/CD8+ T cells and increased expression of B7.1/B7.2 on B cells and antigen-presenting cells in IFNB knockout mice. Conclusions: These results demonstrate that IFN-β plays an important role in immunoregulation of allergic response in mice. The stronger pulmonary inflammation could be a consequence of significantly expanded antigen-specific CD4+ TH2 cells as a result of efficient antigen presentation by antigen-presenting cells and hence increased production of IgE by B cells.