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

Kaiser F, Cook D, Papoutsopoulou S, Rajsbaum R, Wu X, Yang HT, Grant S, Ricciardi-Castagnoli P, Tsichlis PN, Ley SC, O'Garra A.
J Exp Med. 2009 Aug 31;206(9):1863-71. Epub 2009 Aug 10.

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-beta (IFN-beta) and interleukin-10 (IL-10) in these cell types. It has previously been suggested that IFN-beta 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-beta while decreasing IL-10 production by both macrophages and myeloid DCs. In contrast, CpG induction of both IFN-alpha and IFN-beta 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-beta 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.

URL: http://jem.rupress.org/cgi/content/full/206/9/1863

Pub Med: http://www.ncbi.nlm.nih.gov/pubmed/19667062

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