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

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

Research output: Contribution to journalArticle

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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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Myeloid Cells
Dendritic Cells
Interferons
Macrophages
Interleukin-10
Toll-Like Receptors
Mitogen-Activated Protein Kinase 1
Extracellular Signal-Regulated MAP Kinases
Lipopolysaccharides
Transcription Factors
Phosphotransferases
Cytokines
Proteins

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

TPL-2 negatively regulates interferon-β production in macrophages and myeloid dendritic cells. / Kaiser, Frank; Cook, Dorthe; Papoutsopoulou, Stamatia; Rajsbaum Gorodezky, Ricardo; Wu, Xuemei; Yang, Huei Ting; Grant, Susan; Ricciardi-Castagnoli, Paola; Tsichlis, Philip N.; Ley, Steven C.; O'Garra, Anne.

In: Journal of Experimental Medicine, Vol. 206, No. 9, 31.08.2009, p. 1863-1871.

Research output: Contribution to journalArticle

Kaiser, F, Cook, D, Papoutsopoulou, S, Rajsbaum Gorodezky, R, Wu, X, Yang, HT, Grant, S, Ricciardi-Castagnoli, P, Tsichlis, PN, Ley, SC & O'Garra, A 2009, 'TPL-2 negatively regulates interferon-β production in macrophages and myeloid dendritic cells', Journal of Experimental Medicine, vol. 206, no. 9, pp. 1863-1871. https://doi.org/10.1084/jem.20091059
Kaiser, Frank ; Cook, Dorthe ; Papoutsopoulou, Stamatia ; Rajsbaum Gorodezky, Ricardo ; Wu, Xuemei ; Yang, Huei Ting ; Grant, Susan ; Ricciardi-Castagnoli, Paola ; Tsichlis, Philip N. ; Ley, Steven C. ; O'Garra, Anne. / TPL-2 negatively regulates interferon-β production in macrophages and myeloid dendritic cells. In: Journal of Experimental Medicine. 2009 ; Vol. 206, No. 9. pp. 1863-1871.
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