• Citer

Interferon response factor 3 is essential for house dust mite-induced airway allergy

par Marichal, Thomas;Bedoret, Denis;Mesnil, Claire;Pichavant, Muriel;Goriely, Stanislas ;Trottein, François;Cataldo, Didier;Goldman, Michel ;Lekeux, Pierre;Bureau, Fabrice ;Desmet, Christophe
Référence Journal of allergy and clinical immunology, 126, 4, page (836-844.e13)
Publication Publié, 2010-10

Article révisé par les pairs

• Accès en ligne
• Détails
• Contenu
• Statistiques

Résumé :

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. © 2010 American Academy of Allergy, Asthma & Immunology.