IRF-7 is the master regulator of type-I interferon-dependent immune responses

Kenya Honda, Hideyuki Yanai, Hideo Negishi, Masataka Asagiri, Mitsuharu Sato, Tatsuaki Mizutani, Naoya Shimada, Yusuke Ohba, Akinori Takaoka, Nobuaki Yoshida and Tadatsugu Taniguchi ()
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Kenya Honda: University of Tokyo
Hideyuki Yanai: University of Tokyo
Hideo Negishi: University of Tokyo
Masataka Asagiri: University of Tokyo
Mitsuharu Sato: University of Tokyo
Tatsuaki Mizutani: University of Tokyo
Naoya Shimada: University of Tokyo
Yusuke Ohba: University of Tokyo
Akinori Takaoka: University of Tokyo
Nobuaki Yoshida: University of Tokyo
Tadatsugu Taniguchi: University of Tokyo

Nature, 2005, vol. 434, issue 7034, 772-777

Abstract: Abstract The type-I interferon (IFN-α/β) response is critical to immunity against viruses and can be triggered in many cell types by cytosolic detection of viral infection, or in differentiated plasmacytoid dendritic cells by the Toll-like receptor 9 (TLR9) subfamily, which generates signals via the adaptor MyD88 to elicit robust IFN induction1,2,3,4. Using mice deficient in the Irf7 gene (Irf7-/- mice), we show that the transcription factor IRF-7 is essential for the induction of IFN-α/β genes via the virus-activated, MyD88-independent pathway and the TLR-activated, MyD88-dependent pathway. Viral induction of MyD88-independent IFN-α/β genes is severely impaired in Irf7-/- fibroblasts. Consistently, Irf7-/- mice are more vulnerable than Myd88-/- mice to viral infection, and this correlates with a marked decrease in serum IFN levels, indicating the importance of the IRF-7-dependent induction of systemic IFN responses for innate antiviral immunity. Furthermore, robust induction of IFN production by activation of the TLR9 subfamily in plasmacytoid dendritic cells is entirely dependent on IRF-7, and this MyD88–IRF-7 pathway governs the induction of CD8+ T-cell responses. Thus, all elements of IFN responses, whether the systemic production of IFN in innate immunity or the local action of IFN from plasmacytoid dendritic cells in adaptive immunity, are under the control of IRF-7.

Date: 2005
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DOI: 10.1038/nature03464

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