• Register
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.


Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.


Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors.

The activation of Toll-like receptors (TLRs) is central to innate and adaptive immunity. All TLRs use the adaptor MyD88 for signalling, but the mechanisms underlying the MyD88-mediated gene induction programme are as yet not fully understood. Here, we demonstrate that the transcription factor IRF-5 is generally involved downstream of the TLR-MyD88 signalling pathway for gene induction of proinflammatory cytokines, such as interleukin-6 (IL-6), IL-12 and tumour-necrosis factor-alpha. In haematopoietic cells from mice deficient in the Irf5 gene (Irf5-/- mice), the induction of these cytokines by various TLR ligands is severely impaired, whereas interferon-alpha induction is normal. We also provide evidence that IRF-5 interacts with and is activated by MyD88 and TRAF6, and that TLR activation results in the nuclear translocation of IRF-5 to activate cytokine gene transcription. Consistently, Irf5-/- mice show resistance to lethal shock induced by either unmethylated DNA or lipopolysaccharide, which correlates with a marked decrease in the serum levels of proinflammatory cytokines. Thus, our study identifies IRF-5 as a new, principal downstream regulator of the TLR-MyD88 signalling pathway and a potential target of therapeutic intervention to control harmful immune responses.

Pubmed ID: 15665823


  • Takaoka A
  • Yanai H
  • Kondo S
  • Duncan G
  • Negishi H
  • Mizutani T
  • Kano S
  • Honda K
  • Ohba Y
  • Mak TW
  • Taniguchi T



Publication Data

March 10, 2005

Associated Grants


Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Antigens, Differentiation
  • Cytokines
  • Gene Deletion
  • Inflammation
  • Interferon Regulatory Factors
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • Mice
  • Myeloid Differentiation Factor 88
  • Promoter Regions, Genetic
  • RNA, Messenger
  • Receptors, Cell Surface
  • Receptors, Immunologic
  • Shock, Septic
  • Signal Transduction
  • TNF Receptor-Associated Factor 6
  • Toll-Like Receptors
  • Transcription Factors
  • Up-Regulation