Role of IFN regulatory factor 5 transcription factor in antiviral immunity and tumor suppression

Hideyuki Yanai, Hui Min Chen, Takayuki Inuzuka, Seiji Kondo, Tak W. Mak, Akinori Takaoka, Kenya Honda, Tadatsugu Taniguchi

Research output: Contribution to journalArticle

142 Citations (Scopus)

Abstract

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 IRFS 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 (lrf5-/- 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 lrf5-/- mice are highly vulnerable to viral infections, accompanied by a decrease in type I IFN induction in the sera. Furthermore, we show that lrf5-/- 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.

Original languageEnglish
Pages (from-to)3402-3407
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number9
DOIs
Publication statusPublished - 2007 Feb 27
Externally publishedYes

Fingerprint

Antiviral Agents
Immunity
Transcription Factors
Virus Diseases
Neoplasms
Apoptosis
Gene Regulatory Networks
Toll-Like Receptors
Gene Expression Regulation
Cell Cycle Checkpoints
DNA Damage
Fibroblasts
Cytokines
Serum
Genes

Keywords

  • Apoptosis
  • IRF
  • p53

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Role of IFN regulatory factor 5 transcription factor in antiviral immunity and tumor suppression. / Yanai, Hideyuki; Chen, Hui Min; Inuzuka, Takayuki; Kondo, Seiji; Mak, Tak W.; Takaoka, Akinori; Honda, Kenya; Taniguchi, Tadatsugu.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 9, 27.02.2007, p. 3402-3407.

Research output: Contribution to journalArticle

Yanai, Hideyuki ; Chen, Hui Min ; Inuzuka, Takayuki ; Kondo, Seiji ; Mak, Tak W. ; Takaoka, Akinori ; Honda, Kenya ; Taniguchi, Tadatsugu. / Role of IFN regulatory factor 5 transcription factor in antiviral immunity and tumor suppression. In: Proceedings of the National Academy of Sciences of the United States of America. 2007 ; Vol. 104, No. 9. pp. 3402-3407.
@article{7cda9170ff8d49289f4410e22c0f8881,
title = "Role of IFN regulatory factor 5 transcription factor in antiviral immunity and tumor suppression",
abstract = "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 IRFS 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 (lrf5-/- 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 lrf5-/- mice are highly vulnerable to viral infections, accompanied by a decrease in type I IFN induction in the sera. Furthermore, we show that lrf5-/- 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.",
keywords = "Apoptosis, IRF, p53",
author = "Hideyuki Yanai and Chen, {Hui Min} and Takayuki Inuzuka and Seiji Kondo and Mak, {Tak W.} and Akinori Takaoka and Kenya Honda and Tadatsugu Taniguchi",
year = "2007",
month = "2",
day = "27",
doi = "10.1073/pnas.0611559104",
language = "English",
volume = "104",
pages = "3402--3407",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "9",

}

TY - JOUR

T1 - Role of IFN regulatory factor 5 transcription factor in antiviral immunity and tumor suppression

AU - Yanai, Hideyuki

AU - Chen, Hui Min

AU - Inuzuka, Takayuki

AU - Kondo, Seiji

AU - Mak, Tak W.

AU - Takaoka, Akinori

AU - Honda, Kenya

AU - Taniguchi, Tadatsugu

PY - 2007/2/27

Y1 - 2007/2/27

N2 - 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 IRFS 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 (lrf5-/- 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 lrf5-/- mice are highly vulnerable to viral infections, accompanied by a decrease in type I IFN induction in the sera. Furthermore, we show that lrf5-/- 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.

AB - 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 IRFS 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 (lrf5-/- 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 lrf5-/- mice are highly vulnerable to viral infections, accompanied by a decrease in type I IFN induction in the sera. Furthermore, we show that lrf5-/- 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.

KW - Apoptosis

KW - IRF

KW - p53

UR - http://www.scopus.com/inward/record.url?scp=33847645819&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33847645819&partnerID=8YFLogxK

U2 - 10.1073/pnas.0611559104

DO - 10.1073/pnas.0611559104

M3 - Article

C2 - 17360658

AN - SCOPUS:33847645819

VL - 104

SP - 3402

EP - 3407

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 9

ER -