論文 - 詳細
RRC ID | 11803 |
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著者 | Marichal T, Bedoret D, Mesnil C, Pichavant M, Goriely S, Trottein F, Cataldo D, Goldman M, Lekeux P, Bureau F, Desmet CJ. |
タイトル | Interferon response factor 3 is essential for house dust mite-induced airway allergy. |
ジャーナル | J Allergy Clin Immunol |
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 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. |
巻・号 | 126(4) |
ページ | 836-844.e13 |
公開日 | 2010-10-1 |
DOI | 10.1016/j.jaci.2010.06.009 |
PII | S0091-6749(10)00908-5 |
PMID | 20673978 |
MeSH | Animals Antigens, Dermatophagoides / adverse effects Antigens, Dermatophagoides / immunology* Asthma / etiology Asthma / immunology Dendritic Cells / immunology Disease Models, Animal Humans Interferon Regulatory Factor-3 / genetics Interferon Regulatory Factor-3 / metabolism* Interferon Regulatory Factor-7 / genetics Interferon Regulatory Factor-7 / metabolism Mice Mice, Inbred C57BL Mice, Knockout Pyroglyphidae / immunology* Respiratory Hypersensitivity / etiology Respiratory Hypersensitivity / immunology* Th2 Cells / immunology |
IF | 10.228 |
引用数 | 28 |
WOS 分野 | ALLERGY IMMUNOLOGY |
リソース情報 | |
実験動物マウス | RBRC00858 RBRC01420 |