TPL-2 negatively regulates interferon-β production in macrophages and myeloid dendritic cells

Frank Kaiser, Dorthe Cook, Stamatia Papoutsopoulou, Ricardo Rajsbaum, Xuemei Wu, Huei Ting Yang, Susan Grant, Paola Ricciardi-Castagnoli, Philip N. Tsichlis, Steven C. Ley, Anne O'Garra

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111 Scopus citations

Abstract

Stimulation of Toll-like receptors (TLRs) on macrophages and dendritic cells (DCs) by pathogen-derived products induces the production of cytokines, which play an important role in immune responses. Here, we investigated the role of the TPL-2 signaling pathway in TLR induction of interferon-β (IFN-β) and interleukin-10 (IL-10) in these cell types. It has previously been suggested that IFN-β and IL-10 are coordinately regulated after TLR stimulation. However, in the absence of TPL-2 signaling, lipopolysaccharide (TLR4) and CpG (TLR9) stimulation resulted in increased production of IFN-β while decreasing IL-10 production by both macrophages and myeloid DCs. In contrast, CpG induction of both IFN-β and IFN-β by plasmacytoid DCs was decreased in the absence of TPL-2, although extracellular signal-regulated kinase (ERK) activation was blocked. Extracellular signal-related kinase-dependent negative regulation of IFN-β in macrophages was IL-10-independent, required protein synthesis, and was recapitulated in TPL-2-deficient myeloid DCs by retroviral transduction of the ERK-dependent transcription factor c-fos.

Original languageEnglish (US)
Pages (from-to)1863-1871
Number of pages9
JournalJournal of Experimental Medicine
Volume206
Issue number9
DOIs
StatePublished - Aug 31 2009
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Kaiser, F., Cook, D., Papoutsopoulou, S., Rajsbaum, R., Wu, X., Yang, H. T., Grant, S., Ricciardi-Castagnoli, P., Tsichlis, P. N., Ley, S. C., & O'Garra, A. (2009). TPL-2 negatively regulates interferon-β production in macrophages and myeloid dendritic cells. Journal of Experimental Medicine, 206(9), 1863-1871. https://doi.org/10.1084/jem.20091059