Role of IFN regulatory factor 5 transcription factor in antiviral immunity and tumor suppression.
Host defense consists of two main aspects, namely, immune response to invading pathogens and suppression of tumor development. A family of transcription factors, IFN regulatory factors (IRFs), has recently gained much attention in terms of its critical role in linking these two aspects of host defense, wherein IRF5 was previously shown to play a critical role in the induction of proinflammatory cytokines by activation of Toll-like receptors. In the present study, using IRF5 gene-targeted mice (Irf5(-/-) mice), we demonstrate another facet of the IRF5 function in the regulation of immune response and tumor suppression. We show that IRF5 is critical for antiviral immunity by showing that Irf5(-/-) mice are highly vulnerable to viral infections, accompanied by a decrease in type I IFN induction in the sera. Furthermore, we show that Irf5(-/-) fibroblasts are resistant to apoptosis upon viral infection, resulting in an enhanced viral propagation. Finally, we provide evidence that IRF5 is critical for the induction of apoptosis, but not in cell cycle arrest, in response to DNA damage and that IRF5 functions as a tumor suppressor by acting on a pathway that may be distinct from that for p53. These results, together with the dual regulation of IRF5 gene expression by IFN signaling and p53, may provide a new link in the transcriptional network underlying antiviral immunity and tumor suppression.
Yanai
Hideyuki
H
Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
Chen
Hui-Min
HM
Inuzuka
Takayuki
T
Kondo
Seiji
S
Mak
Tak W
TW
Takaoka
Akinori
A
Honda
Kenya
K
Taniguchi
Tadatsugu
T
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D002453:Cell Cycle / Q000276:immunology; D017931:DNA Primers; D005786:Gene Expression Regulation / Q000276:immunology*; D050835:Interferon Regulatory Factors / Q000276:immunology*; D015850:Interleukin-6 / Q000097:blood; D008264:Macrophages / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000276:immunology; D014777:Virus Diseases / Q000235:genetics / Q000276:immunology*
D017931:DNA Primers; D050835:Interferon Regulatory Factors; D015850:Interleukin-6; C498178:Irf5 protein, mouse; D025521:Tumor Suppressor Proteins