Mouse anti-Human ISGF3γ monoclonal antibody, clone 7/JTHG4γ

IFN beta exerts its activity through the interaction with IFNAR, through activation of the JAK/STAT pathway. We analyzed the changes in IFNAR1, IFNAR2, STAT1, STAT2, Tyk2, JAK1, IRF9 and MxA gene expressions after prolonged IFN beta treatment, in isolated mononuclear-cell subpopulations from MS patients, by real time PCR. The effect of IFN beta on gene expression differed depending on the subpopulation assessed. The data suggest that CD8+ T cells are the most influenced by prolonged IFN beta therapy as IFNAR2, Tyk2, IRF9 and Jak1 expressions were decreased, whereas MxA expression was increased in these cells. (C) 2010 Elsevier B.V. All rights reserved.

In myeloid dendritic cells, activation of the IL-27p28 gene is selectively induced by ligands of TLR4 or TLR3, both coupled to the Toll/IL-1R-related domain-containing adaptor-inducing IFN/IFN regulatory factor (IRF)3 pathway. In response to both ligands, autocrine type I IFN production was required for optimal IL-27p28 expression. Type I IFN signaling was necessary for sustained IRF1 activation and formation of the IRF9-containing IFN-stimulated gene factor 3 complex. Indeed, we demonstrated that IRFI and IRF9 are sequentially activated and recruited to the IL-27p28 IFN-stimulated regulatory element site. Involvement of IRF1 and IRF9 in the induction of IL-27p28 was confirmed in vitro and upon in vivo exposure to TLR ligands. Thus, in response to TLR4 or TLR3 ligation, the initial induction of the IL-27p28 gene depends on the recruitment of IRF1 and IRF3, whereas transcriptional amplification requires recruitment of the IFN-stimulated gene factor 3 complex. These results highlight the complex molecular interplay between TLRs and type I IFNs for the control of IL-27 synthesis. The Journal of Immunology, 2010, 184: 1784-1792.