Interferon response factor 3 is essential for house dust mite-induced airway allergy.
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.
Marichal
Thomas
T
Laboratory of Cellular and Molecular Physiology, GIGA-Research and Faculty of Veterinary Medicine, University of Liege, Liege, Belgium.
Bedoret
Denis
D
Mesnil
Claire
C
Pichavant
Muriel
M
Goriely
Stanislas
S
Trottein
François
F
Cataldo
Didier
D
Goldman
Michel
M
Lekeux
Pierre
P
Bureau
Fabrice
F
Desmet
Christophe J
CJ
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
D039741:Antigens, Dermatophagoides; D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7