| First Author | Marichal T | Year | 2010 |
| Journal | J Allergy Clin Immunol | Volume | 126 |
| Issue | 4 | Pages | 836-844.e13 |
| PubMed ID | 20673978 | Mgi Jnum | J:305134 |
| Mgi Id | MGI:6511398 | Doi | 10.1016/j.jaci.2010.06.009 |
| Citation | Marichal T, et al. (2010) Interferon response factor 3 is essential for house dust mite-induced airway allergy. J Allergy Clin Immunol 126(4):836-844.e13 |
| abstractText | 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. |
