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

Authors: Marichal, T  Bedoret, D  Mesnil, C  Pichavant, M  Goriely, S  Trottein, F  Cataldo, D  Goldman, M  Lekeux, P  Bureau, F  Desmet, CJ 
Citation: Marichal T, etal., J Allergy Clin Immunol. 2010 Oct;126(4):836-844.e13. Epub 2010 Jul 31.
Pubmed: (View Article at PubMed) PMID:20673978
DOI: Full-text: DOI:10.1016/j.jaci.2010.06.009

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. CONCLUSION: 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.


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CRRD Object Information
CRRD ID: 5128793
Created: 2011-03-16
Species: All species
Last Modified: 2011-03-16
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.