title: Interferon response factor 3 is essential for house dust mite-induced airway allergy.
abstract: BACKGROUND
  Pattern-recognition receptors (PRRs) are critically involved in the pathophysiology of airway allergy, yet most of the signaling pathways downstream of PRRs implicated in allergic airway sensitization remain unknown.
  
  
  OBJECTIVE
  We sought to study the effects of genetic depletion of interferon response factor (IRF) 3 and IRF7, important transcription factors downstream of various PRRs, in a murine model of house dust mite (HDM)-induced allergic asthma.
  
  
  METHODS
  We compared HDM-induced allergic immune responses in IRF3-deficient (IRF3(-/-)), IRF7(-/-), and wild-type mice.
  
  
  RESULTS
  Parameters of airway allergy caused by HDM exposure were strongly attenuated in IRF3(-/-), but not IRF7(-/-), mice compared with those in wild-type mice. Indeed, in HDM-exposed IRF3(-/-) mice HDM-specific T(H)2 cell responses did not develop. This correlated with impaired maturation and migration of IRF3(-/-) lung dendritic cells (DCs) on HDM treatment. Furthermore, adoptive transfer of HDM-loaded DCs indicated that IRF3(-/-) DCs had an intrinsic defect rendering them unable to migrate and to prime HDM-specific T(H)2 responses. Intriguingly, we also show that DC function and allergic airway sensitization in response to HDM were independent of signaling by type I interferons, the main target genes of IRF3.
  
  
  CONCLUSIONS
  Through its role in DC function, IRF3, mainly known as a central activator of antiviral immunity, is essential for the development of T(H)2-type responses to airway allergens.
authors.affiliation: Laboratory of Cellular and Molecular Physiology, GIGA-Research and Faculty of Veterinary Medicine, University of Liege, Liege, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: Marichal
authors.forename: Denis
authors.initials: D
authors.lastname: Bedoret
authors.forename: Claire
authors.initials: C
authors.lastname: Mesnil
authors.forename: Muriel
authors.initials: M
authors.lastname: Pichavant
authors.forename: Stanislas
authors.initials: S
authors.lastname: Goriely
authors.forename: François
authors.initials: F
authors.lastname: Trottein
authors.forename: Didier
authors.initials: D
authors.lastname: Cataldo
authors.forename: Michel
authors.initials: M
authors.lastname: Goldman
authors.forename: Pierre
authors.initials: P
authors.lastname: Lekeux
authors.forename: Fabrice
authors.initials: F
authors.lastname: Bureau
authors.forename: Christophe J
authors.initials: CJ
authors.lastname: Desmet
mesh_terms: D000818:Animals; D039741:Antigens, Dermatophagoides / Q000009:adverse effects / Q000276:immunology*; D001249:Asthma / Q000209:etiology / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000378:metabolism*; D050839:Interferon Regulatory Factor-7 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D039981:Pyroglyphidae / Q000276:immunology*; D012130:Respiratory Hypersensitivity / Q000209:etiology / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
chemical_list: D039741:Antigens, Dermatophagoides; D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7