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• W2019913536 endingPage "779" @default.
• W2019913536 startingPage "770" @default.
• W2019913536 abstract "Both type I interferon (IFN-α/β) and type II IFN (IFN-γ) exert many functions that are restricted to immune cells. Thus, they play critical roles in innate and adaptive immunity. IFN regulatory factor-4 (IRF-4) and IRF-8 (formerly PU.1 interaction partner [Pip] and IFN consensus sequence binding domain [ICSBP], respectively) are immune cell-specific members of the IRF family that regulate the development of myeloid, lymphoid, and dendritic cells. They form a heterodimeric complex with another immune cell-specific transcription factor PU.1-Spi-1 and regulate transcription of genes in the immune system. This review describes the role of the IRF-8-PU.1 complex in modulating IFN signaling in an immune cell-specific manner. Our studies revealed that some but not all IFN-γ-inducible genes carry an IFN-γ activation site (GAS) element that contains a binding site for the IRF- 8-PU.1 complex. The IRF-8-PU.1 complex can take part in GAS-mediated transcription and amplify expression of IFN-γ-responsive genes initiated by Stat1 in macrophages. Similarly, some but not all IFN-α/β-responsive genes are shown to carry an IFN-stimulated response element (ISRE) that contains an IRF-8-PU.1 binding site. The participation of IRF-8-PU.1 in ISRE-mediated transcription results in the augmentation of IFN-stimulated gene factor 3 (ISGF3)-induced transcription in macrophages. Thus, GAS and ISRE elements, classically defined as universal IFN-α/β and IFN-γ response sequences, are not the same, and some harbor an embedded motif for IRF- 8-PU.1 binding that functions only in immune cells. Accordingly, the IRF-8-PU.1complex provides secondary IFN signaling pathways unique to the immune system. Collectively, the contribution of IRF-8 and PU.1 to IFN-regulated gene expression may in part account for immune cell-specific functions of IFNs." @default.
• W2019913536 created "2016-06-24" @default.
• W2019913536 creator A5011086611 @default.
• W2019913536 creator A5033861845 @default.
• W2019913536 creator A5050855780 @default.
• W2019913536 creator A5066948884 @default.
• W2019913536 date "2005-12-01" @default.
• W2019913536 modified "2023-10-18" @default.
• W2019913536 title "Immune Cell-Specific Amplification of Interferon Signaling by the IRF-4/8-PU.1 Complex" @default.
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• W2019913536 doi "https://doi.org/10.1089/jir.2005.25.770" @default.
• W2019913536 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16375605" @default.
• W2019913536 hasPublicationYear "2005" @default.
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