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

Youzhong Wan, Tae Whan Kim, Minjia Yu, Hao Zhou, Michifumi Yamashita, Zizhen Kang, Weiguo Yin, Jian An Wang, James Thomas, Ganes C. Sen, George R. Stark, Xiaoxia Li

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3006-3014
Number of pages9
JournalJournal of Immunology
Volume186
Issue number5
DOIs
StatePublished - Mar 1 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Wan, Y., Kim, T. W., Yu, M., Zhou, H., Yamashita, M., Kang, Z., Yin, W., Wang, J. A., Thomas, J., Sen, G. C., Stark, G. R., & Li, X. (2011). The dual functions of IL-1 receptor-associated kinase 2 in TLR9-mediated IFN and proinflammatory cytokine production. Journal of Immunology, 186(5), 3006-3014. https://doi.org/10.4049/jimmunol.1003217