title: IL-27 and IFN-alpha signal via Stat1 and Stat3 and induce T-Bet and IL-12Rbeta2 in naive T cells.
abstract: Interleukin-27 (IL-27) supports proliferation of naive CD4(+) T cells and enhances interferon-gamma (IFN-gamma) production by activated T cells and natural killer (NK) cells. We report here that IL-27 induces Stat1 and Stat3 phosphorylation and activation in human and murine cell lines and primary human T cells. IL-27 also induces T-Bet, a Stat1-dependent gene crucial to Th1 cell commitment. Similarly, IFN-alpha activates Stat1 and Stat3 and T-Bet expression in naive T cells. Induction of T-Bet results in upregulation of IL-12Rbeta2 on naive T cells, which is essential for responsiveness to IL-12 and differentiation to a Th1 phenotype. Both IL-27 and IFN-alpha induce expression of IL-12Rbeta2 in T cells. In contrast, IFN-gamma, which activates Stat1 but not Stat3, induces expression of T-Bet but not IL-12Rbeta2 in naive T cells. We propose that IL-27 and IFN-alpha are important for early Th1 commitment and act upstream of IL-12 and IFN-gamma in this pathway.
authors.affiliation: Department of Discovery Biology, DNAX Research Institute, Palo Alto, CA 94304, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Hibbert
authors.forename: Stefan
authors.initials: S
authors.lastname: Pflanz
authors.forename: Rene
authors.initials: R
authors.lastname: De Waal Malefyt
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kastelein
mesh_terms: D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology / Q000378:metabolism*; D007378:Interleukins / Q000276:immunology / Q000378:metabolism*; D010766:Phosphorylation; D018123:Receptors, Interleukin / Q000378:metabolism*; D053707:Receptors, Interleukin-12; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D020825:T-Box Domain Proteins; D013601:T-Lymphocytes / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D000098815:T-bet Transcription Factor
chemical_list: D004268:DNA-Binding Proteins; D016898:Interferon-alpha; D007378:Interleukins; C464565:MYDGF protein, human; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors