title: Upregulation of B7 molecules (CD80 and CD86) and exacerbated eosinophilic pulmonary inflammatory response in mice lacking the IFN-beta gene.
abstract: BACKGROUND
  IFN-beta has been shown to be effective as therapy for multiple sclerosis. Some reports attributed its beneficial effects to the capacity to induce a T(H)2 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-beta in controlling the development of allergic inflammation.
  
  
  METHODS
  We assessed whether deletion of the gene encoding IFN-beta (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-beta+/-), whereas no differences were observed in regard to local levels of IFN-gamma. Moreover, systemic response with IgE production is also enhanced. Lack of IFN-beta 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-gamma 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-beta 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+ T(H)2 cells as a result of efficient antigen presentation by antigen-presenting cells and hence increased production of IgE by B cells.
authors.affiliation: Section for Medical Inflammation Research, Institute for Cell and Molecular Biology, Lund University, Lund, Sweden.
authors.forename: Victor
authors.initials: V
authors.lastname: Matheu
authors.forename: Alexandra
authors.initials: A
authors.lastname: Treschow
authors.forename: Vaidrius
authors.initials: V
authors.lastname: Navikas
authors.forename: Shohreh
authors.initials: S
authors.lastname: Issazadeh-Navikas
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D018122:B7-1 Antigen / Q000378:metabolism*; D051940:B7-2 Antigen; D001773:Blood Cells / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D000939:Epitopes; D007107:Immune System / Q000166:cytology / Q000378:metabolism; D007073:Immunoglobulin E / Q000032:analysis / Q000378:metabolism; D016899:Interferon-beta / Q000172:deficiency* / Q000235:genetics; D007378:Interleukins / Q000032:analysis; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D010047:Ovalbumin / Q000276:immunology; D011657:Pulmonary Eosinophilia / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D000939:Epitopes; D007378:Interleukins; D008562:Membrane Glycoproteins; D007073:Immunoglobulin E; D016899:Interferon-beta; D010047:Ovalbumin