Genome-wide effect of constitutive IFN-signaling
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA434236 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Using wild type mice and mice deficient for either IFNb1 or IFN-receptor, we analysed the effect of the constitutive IFN on genome-wide expression
2018-06-01 | GSE110678 | GEO
Project description:Using mice deficient for several genes that contribute to constitutive levels of type I interferon, we compared genome-wide expressionof RNA in rested macrophages of these mice.
2017-06-29 | GSE83885 | GEO
Project description:Microarray analysis was designed to study the effect of PIAS1 on interferon (IFN) signaling pathway by comparing the gene activation profiles of wild type and Pias1 null cells in response to IFN treatments. Microarray analysis was performed essentially following the manufacturer's instructions (Affymetrix). Briefly, bone marrow-derived macrophages (BMMs) from wile type or Pias1 null littermates were either untreated, or treated with IFN-beta (500 U/ml) or IFN-gamma (10 ng/ml) for 2h or 4h. Total RNA was prepared with RNA-STAT60 (TEL-TEST) and purified with the RNeasy kit (Qiagen). Double stranded complementary DNA was synthesized from 20 ug of total RNA according to Affymetrix methodology, and purified with Phase Lock Gels (Eppendorf). Biotin-labeled RNA was synthesized with the BioArray High Yield RNA Transcript Labeling Kit (Enzo). Samples were cleaned, fragmentated and hybridized to murine genome (MGU74Av2) Genechips (Affymetrix) as instructed. GeneChips were stained with phycoerythrin-streptavidin (Molecular Probes) and scanned with a GeneChip scanner (Affymetrix).
2007-10-10 | E-GEOD-1552 | biostudies-arrayexpress
Project description:Type III interferons (IFN-λ) are antiviral and immunomodulatory cytokines that have been best characterized in respiratory and gastrointestinal infections, but the effects of IFN-λ against skin infections have not been extensively investigated. We sought to define the skin-specific effects of IFN-λ against the highly prevalent human pathogen herpes simplex virus (HSV). We infected mice lacking the IFN-λ receptor (Ifnlr1-/-), both the IFN-λ and the IFN-αβ receptor (Ifnar1-/- Ifnlr1-/-), or IFN-λ cytokines (Ifnl2/3-/-) and found that IFN-λ restricts the severity of HSV-1 and HSV-2 skin lesions, independent of a direct effect on viral load. Using conditional knockout mice, we found that IFN-λ signaling in both keratinocytes and neutrophils was necessary to control HSV-1 skin lesion severity, and that IFN-λ signaling in keratinocytes suppressed CXCL9-mediated neutrophil recruitment to the skin. Furthermore, depleting neutrophils prevented the development of severe HSV-1 skin lesions in Ifnlr1-/- mice. Altogether, our results suggest that IFN-λ plays an immunomodulatory role in the skin that restricts neutrophil-mediated pathology during HSV infection, and suggest potential applications for IFN-λ in treating viral skin infections.
2023-09-12 | GSE242170 | GEO
Project description:Type III interferons (IFN-λ) are antiviral and immunomodulatory cytokines that have been best characterized in respiratory and gastrointestinal infections, but the effects of IFN-λ against skin infections have not been extensively investigated. We sought to define the skin-specific effects of IFN-λ against the highly prevalent human pathogen herpes simplex virus (HSV). We infected mice lacking the IFN-λ receptor (Ifnlr1-/-), both the IFN-λ and the IFN-αβ receptor (Ifnar1-/- Ifnlr1-/-), or IFN-λ cytokines (Ifnl2/3-/-) and found that IFN-λ restricts the severity of HSV-1 and HSV-2 skin lesions, independent of a direct effect on viral load. Using conditional knockout mice, we found that IFN-λ signaling in both keratinocytes and neutrophils was necessary to control HSV-1 skin lesion severity, and that IFN-λ signaling in keratinocytes suppressed CXCL9-mediated neutrophil recruitment to the skin. Furthermore, depleting neutrophils prevented the development of severe HSV-1 skin lesions in Ifnlr1-/- mice. Altogether, our results suggest that IFN-λ plays an immunomodulatory role in the skin that restricts neutrophil-mediated pathology during HSV infection, and suggest potential applications for IFN-λ in treating viral skin infections.
2023-09-12 | GSE242068 | GEO
Project description:The critical role of type I IFN (IFN I ) in viral disease is thoroughly documented while their function in bacterial infection remains ambiguous. General interest in biological functions of IFN I in Mycobacterium tuberculosis (Mtb) infection was raised by the identification of a distinct IFN I gene expression signature in tuberculosis (TB) patients. Here we demonstrate that TB-susceptible mice lacking the receptor for IFN I (IFNAR1) were protected from death upon aerogenic infection with Mtb. Increased survival was accompanied by reduced bacterial burden and ameliorated lung pathology as well as diminished production of proinflammatory IL-1?, among other cytokines. IFNAR1 signaling did not affect T cell responses, but markedly altered migration of inflammatory monocytes and neutrophils to the lung during pulmonary TB. This process was orchestrated by presence of IFNAR1 in both immune and tissue-resident radioresistant cells. IFNAR1-driven TB susceptibility was initiated by CXCL5/CXCL1-driven accumulation of neutrophils into alveoli and subsequently a distinct compartmentalization of Mtb in lung phagocytes. We conclude that IFN I alters early innate events at the site of Mtb invasion leading to unleashed inflammation. Hence, our data furnish a mechanistic explanation for the detrimental role of IFN I in pulmonary TB. dual-color color-swap
2013-12-31 | E-GEOD-44848 | biostudies-arrayexpress
Project description:The RIG-I-like receptors (RLRs) form filaments to activate type-I interferon (IFN-I) and NF-KB signaling through their adaptor protein MAVS and downstream cascades. These filaments are recognized and regulated by cell-encoded machinery for correct activation. Here, we identified the stress-sensitive heat shock protein, HSPA6, was induced to express upon RLR-MAVS activation to act as a negative regulator of IFN-I signaling. Interestingly, by using MAVS-KO cells, we showed that HSPA6 was upregulated dependent on the presence of IFN-competent RLRs but not MAVS. Gene knockout (KO) tests indicated that the E3 ligases, stress granules (SGs), and transcription factors IRF1 and AP1 were all shared to induce HSPA6 and the canonical IFNb. Kinetic analysis showed that HSPA6 upregulated slower than IFNb, implicating these two genes competed machinery for transcription activation. Further tests suggested the induced HSPA6 bound to IFN-competent MDA5 to dissolve the filaments and downregulated IFN induction. Thus, our study uncovered a new gene activation mechanism by the IFN-competent RLRs to serve as negative feedback, arguing for a gene regulatory role of functional filaments of innate immunity.
2024-01-01 | GSE252140 | GEO
Project description:Type I IFN-signaling suppresses an excessive IFN-{gamma} response and prevents lung damage and chronic inflammation following Pneumocystis (PC)-infection and clearance in CD4 T cell-competent mice. Type I IFN -signaling in pulmonary CD11c+ DCs and alveolar macrophages may prevent chronic inflammation following PC lung infection and clearance by suppressing an excessive IFN-g-response via the induction of SOCS1. IFNAR-/- and wildtype mice were both Pneumocystis infected via itratracheal instillation. Pulmonary CD11c+ cells were isolated from collagen digested lungs at day 7 and day 14 post infection from both wildtype and IFNAR-/- mice using a magnetic cell sorting technique from Miltenyi with CD11c microbeads. Cells from three individual animals per group were isolated and assessed. Comparison of 2 treatment types at 2 timepoints to determine whether type I IFN signaling is initiated in resident and early recruited pulmonary CD11c+ cells following Pneumocystis lung infection and whether this is relevant to the outcome of the inflammatory response during the initiation of clearance.
2010-07-07 | E-GEOD-18607 | biostudies-arrayexpress
Project description:To investigate the RNA differences in muscle with and without constitutive AHR activation. AAV9 was used to express either a green fluorescent protein (control) or mutant AHR protein that exhibits constitutive transcriptional activity
2023-06-08 | GSE225607 | GEO
Project description:Using genome-wide sequencing approaches we viewed the contributions of Toll-like receptor 7 (TLR7) and type I interferon (IFN-I) in the regulation of coding and noncoding RNA expression in CAL-1 pDC treated with R848 or IFNβ. Functional enrichment analysis revealed both the unique and synergistic roles of TLR7 and IFN-I signaling in the orchestration of pDC function.
2019-03-21 | GSE117127 | GEO