Interferon response factor 3 is essential for house dust mite–induced airway allergy - 07/08/11
, Denis Bedoret, DVM, PhD a, , Claire Mesnil, DVM a, Muriel Pichavant, PhD b, Stanislas Goriely, PhD c, François Trottein, PhD b, Didier Cataldo, MD, PhD d, Michel Goldman, MD, PhD c, Pierre Lekeux, DVM, PhD a, Fabrice Bureau, DVM, PhD a, ⁎ 
, Christophe J. Desmet, PhD a, ⁎ Reprint requests: Christophe J. Desmet, PhD, or Fabrice Bureau, DVM, PhD, Laboratory of Molecular and Cellular Physiology, GIGA-Research, University of Liege, 4000 Liege, Belgium.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 TH2 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 TH2 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.
Conclusion |
Through its role in DC function, IRF3, mainly known as a central activator of antiviral immunity, is essential for the development of TH2-type responses to airway allergens.
Le texte complet de cet article est disponible en PDF.Key words : Airway allergy, interferon response factor 3, interferon response factor 7, dendritic cell, type I interferon
Abbreviations used : BLN, BMDC, CFSE, DC, HDM, IFNAR2, IRF, MyD88, OVA, PRR, TLR, TRIF, WT
Plan
| The Laboratory of Cellular and Molecular Physiology is supported by grants of the Fonds National de la Recherche Scientifique (FNRS; Belgium; Mandat d’Impulsion Scientifique), by the Fonds de la Recherche Scientifique Médicale (FRSM; Belgium), and by the Belgian Programme on Interuniversity Attraction Poles (IUAP; FEDIMMUNE) initiated by the Belgian State (Belgian Science Policy). T.M., D.B., and C.M. are research fellows, C.J.D. is a postdoctoral researcher, and S.G. is research associate of the National Fund for Scientific Research Belgium (FRS-FNRS, Belgium). |
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| Disclosure of potential conflict of interest: D. Cataldo has received grants from Fonds National de la Recherche Scientifique (FNRS) and Walloon Regional Government (Belgium). |
Vol 126 - N° 4
P. 836 - octobre 2010 Retour au numéro
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