Mar 23, 2021 · We find that TLR4 signaling in macrophages uniquely engages transcription factor IRF1, which facilitates the opening of ISG loci for transcription. This study provides a critical mechanistic basis for lineage-specific TLR responses and uncovers IRF1 as a master regulator for the ISG transcriptional program in human macrophages.

Taken together, we postulate that IRF-1 hyper-activation and elevated STAT1 dimer formation associate with enhanced expression of a subset of interferon stimulated genes (ISGs) which may lead to even greater antiviral activity.

Jan 21, 2021 · Thus, IRF1 fits the typical profile of an “IFN-stimulated gene” (ISG). Both IRF1 mRNA transcripts and the IRF1 protein itself are short-lived [14], allowing for rapid, dynamic regulation in response to infection.

Mar 23, 2021 · We find that TLR4 signaling in macrophages uniquely engages transcription factor IRF1, which facilitates the opening of ISG loci for transcription. This study provides a critical mechanistic basis for lineage-specific TLR responses and uncovers IRF1 as a master regulator for the ISG transcriptional program in human macrophages.

Using an IRF1-deficient BEAS-2B cell line, we demonstrate that: (1) In response to PRR stimulation, IRF1 supports early expression of IFNβ and IFNλ1/2, STAT1/2 activation, and ISG expression; (2) IRF1 mediates IFN-independent antiviral immunity by supporting constitutive expression of antiviral effectors as well as PRRs that support IRF3 ...

Apr 24, 2024 · Mechanistically, we describe the specific input of ISGF3 and IRF1 into enhancer activation and the regulation of chromatin accessibility at interferon-stimulated genes (ISG). We further report differences between the IFN types in altering RNA …

IRF-1 regulates expression of target genes by binding to an interferon stimulated response element (ISRE) in their promoters. The IRF-1 protein binds to the ISRE via an N-terminal helix-turn-helix DNA binding domain, [7] which is highly conserved among all IRF proteins.

We find that TLR4 signaling in macrophages uniquely engages transcription factor IRF1, which facilitates the opening of ISG loci for transcription. This study provides a critical mechanistic basis for lineage-specific TLR re-sponses and uncovers IRF1 as a master regulator for the ISG transcriptional program in human macro-phages.

Dec 23, 2013 · Type I interferon (IFN) responses are regulated by host, pathogen and environmental factors. These factors calibrate the host defences while limiting tissue damage and preventing autoimmunity.

Feb 15, 2018 · In this study, we demonstrate the role of IFN regulatory factor (IRF)1 in promoting NLRP3 inflammasome activation and cell death during IAV infection. Both inflammasome-dependent responses and induction of apoptosis and necroptosis are reduced in cells lacking IRF1 infected with IAV.