Previous Article |
Table of Contents
| Next Article 
BIOLOGICAL SCIENCES / IMMUNOLOGY
Role of IFN regulatory factor 5 transcription factor in antiviral immunity and tumor suppression
*Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan; Department of Veterinary Internal Medicine, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan; and Campbell Family Institute of Breast Cancer Research, University of Toronto, University Avenue, Room 7-411, Toronto, ON, Canada M5G 2M9
Contributed by Tadatsugu Taniguchi, December 26, 2006 (received for review December 25, 2006)
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.
apoptosis | IRF | p53
The authors declare no conflict of interest.
This article contains supporting information online at www.pnas.org/cgi/content/full/0611559104/DC1.
To whom correspondence should be addressed. E-mail: tada{at}m.u-tokyo.ac.jp
© 2007 by The National Academy of Sciences of the USA
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg What's this?
This article has been cited by other articles in HighWire Press-hosted journals:
|
|
 |
|
  S. Sigurdsson, H. H.H. Goring, G. Kristjansdottir, L. Milani, G. Nordmark, J. K. Sandling, M.-L. Eloranta, D. Feng, N. Sangster-Guity, I. Gunnarsson, et al. Comprehensive evaluation of the genetic variants of interferon regulatory factor 5 (IRF5) reveals a novel 5 bp length polymorphism as strong risk factor for systemic lupus erythematosus Hum. Mol. Genet., March 15, 2008; 17(6): 872 - 881. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Couzinet, K. Tamura, H.-m. Chen, K. Nishimura, Z. Wang, Y. Morishita, K. Takeda, H. Yagita, H. Yanai, T. Taniguchi, et al. A cell-type-specific requirement for IFN regulatory factor 5 (IRF5) in Fas-induced apoptosis PNAS, February 19, 2008; 105(7): 2556 - 2561. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. E. Randall and S. Goodbourn Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures J. Gen. Virol., January 1, 2008; 89(1): 1 - 47. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. J. Martin, J. M. Lee, D. Walls, and S. D. Hayward Manipulation of the Toll-Like Receptor 7 Signaling Pathway by Epstein-Barr Virus J. Virol., September 15, 2007; 81(18): 9748 - 9758. [Abstract] [Full Text] [PDF]
|
|
