IL-27 regulates IL-12 responsiveness of naïve CD4+ T cells through Stat1-dependent and -independent mechanisms
AUTOR(ES)
Lucas, Sophie
FONTE
National Academy of Sciences
RESUMO
IL-27, a novel heterodimeric cytokine produced by antigen-presenting cells, signals through the T cell cytokine receptor (TCCR)/WSX-1 expressed on naïve CD4+ T cells and natural killer cells. TCCR/WSX-1 deficiency results in delayed T helper type 1 (TH1) development through an unresolved mechanism. We report here that IL-27 stimulation in developing murine T helper cells potently induces the expression of the major TH1-specific transcription factor T-bet and its downstream target IL-12R β2, independently of IFNγ. In addition, IL-27 suppresses basal expression of GATA-3, the critical TH2-specific transcription factor that inhibits TH1 development by down-regulating signal transducer and activator of transcription (Stat) 4. IL-27 signaling through TCCR/WSX-1 induces phosphorylation of Stat1, Stat3, Stat4, and Stat5. Stat1 is required for suppression of GATA-3, but T-bet induction by IL-27 can also be mediated through a Stat1-independent pathway. Despite its TH1-like signaling profile, IL-27 is not sufficient to drive the differentiation of CD4+ T cells into IFNγ-producing cells. Similarly, IL-27 induces T-bet expression in primary natural killer cells, but this does not result in an increase of IFNγ production or cytotoxic activity. Therefore, although IL-27 is unable to drive IFNγ production on its own, it plays an important role in the early steps of TH1 commitment by contributing in a paracrine manner to the control of IL-12 responsiveness.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=299900Documentos Relacionados
- Regulation of c–myc expression by IFN–γ through Stat1-dependent and -independent pathways
- The Ets transcription factor ERM is Th1-specific and induced by IL-12 through a Stat4-dependent pathway
- CD4+ and CD8+ T-cell-dependent and -independent host defense mechanisms can operate to control and resolve primary and secondary Francisella tularensis LVS infection in mice.
- IL-1α, IL-1β, and IFN-γ mark β cells for Fas-dependent destruction by diabetogenic CD4+ T lymphocytes
- Naive idiotype-specific CD4+ T cells and immunosurveillance of B-cell tumors.