The dual functions of IL-1 receptor-associated kinase 2 in TLR9-mediated IFN and proinflammatory cytokine production Academic Article uri icon


MeSH Major

  • Cytokines
  • Inflammation Mediators
  • Interferon Type I
  • Interferon-beta
  • Interleukin-1 Receptor-Associated Kinases
  • Toll-Like Receptor 9


  • Bone marrow-derived plasmacytoid dendritic cells (pDCs) from IL-1R-associated kinase (IRAK)2-deficient mice produced more IFNs than did wild-type pDCs upon stimulation with the TLR9 ligand CpG. Furthermore, in CpG-stimulated IRAK2-deficient pDCs there was increased nuclear translocation of IFN regulatory factor 7, the key transcription factor for IFN gene transcription in these cells. In IRAK2-deficient macrophages, enhanced NF-κB activation and increased expression of CpG-induced genes were detected within 2 h after treatment. However, at later times, NF-κB activation was decreased and, in contrast to the results with IFN, there was less secretion of other proinflammatory cytokines (such as TNF-α) and chemokines in CpG-stimulated IRAK2-deficient pDCs and macrophages. Therefore, although IRAK2 is a negative regulator of TLR9-mediated IFN production through its modulation of the transcriptional activity of IFN regulatory factor 7, it is also a positive regulator of TLR9-mediated proinflammatory cytokine and chemokine production at some level subsequent to transcription.

publication date

  • March 2011



  • Academic Article



  • eng

PubMed Central ID

  • PMC3163905

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.1003217

PubMed ID

  • 21270393

Additional Document Info

start page

  • 3006

end page

  • 14


  • 186


  • 5