Type I interferome in human gut CD4 T cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE156844 | GEO | 2020/10/02
REPOSITORIES: GEO
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Project description:Rationale: Humans encode 12 different IFNa proteins. All of them, except IFNa1 (only binds with IFNAR1), bind with IFNAR1 and IFNAR2 to activate their downstream functions. Currently in the field, it is still a debate whether there are qualitative difference between different IFNa subtypes or the differences are merely quantitative. The current study was set out to elucidate the question. Methods: Commercially purchased PBMCs from 7 donors were mock treated or with ISRE activity normalized IFNa1, IFNa2, IFNa4, IFNa5, IFNa8, IFNa14, or IFNb. RNAs were extracted from cells after 18 hrs of incubation. RNASeq libraries were generated using Lexogen Quant Seq 3’ mRNA-Seq library (FWD) Prep Kit. RNASeq were performed on Illumina NovaSEQ6000. Results: An average of 12.6 million gene counts were identified for each donor/treatment. A total of 50,133 genes were mapped, and among them 333 genes were differentially expressed due to type I interferon treatments. Each of IFNa subtypes or IFNb has their specifically regulated genes in PBMCs. Conclusion: These are the further evidences that there are qualitative differences between type I interferons.
2023-12-01 | GSE191317 | GEO
Project description:Interventions: OR7C1+IFNb
BORIS+IFNb
OR7C1+IFNa
BORIS+IFNa
Primary outcome(s): 1) Safety 2) Immunological response
Study Design: Parallel Non-randomized
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Project description:Interferon tau (IFNT), a Type I IFN similar to alpha IFNs (IFNA), is the pregnancy recognition signal, produced by the ruminant conceptus. To elucidate specific effects of bovine IFNT and of other conceptus-derived factors, endometrial gene expression changes during early pregnancy were compared to gene expression changes after intrauterine application of human IFNA2. In study one, endometrial tissue samples were obtained on days (D) 12, 15, and 18 post-mating from nonpregnant or pregnant heifers. In study two, heifers were treated from D14 to D16 of the estrous cycle with an intrauterine device releasing IFNA2 or placebo lipid extrudates or PBS only as controls. Endometrial biopsies were collected after flushing the uterus. All samples from both experiments were analyzed with an Affymetrix Bovine Genome Array. Study one revealed differential gene expression between pregnant and nonpregnant endometria on D15 and D18. In study two, IFNA2 treatment resulted in differential gene expression in the bovine endometrium. Comparison of the datasets from both studies identified genes that were differentially expressed in response to IFNA2 but not in response to pregnancy on D15 or D18. Vice versa, genes were found as differentially expressed during pregnancy but not after IFNA2 treatment. In study three, spatiotemporal alterations in expression of selected genes were determined in uteri from nonpregnant and early pregnant heifers using in situ hybridization. The findings of this study suggest differential effects of bovine IFNT compared to human IFNA2 and that some pregnancy-specific changes in the endometrium are elicited by conceptus-derived factors other than IFNT. Study I: Early pregnancy; day 12 of pregnancy (n=5 heifers), day 15 of pregnancy (n=3), day 18 of pregnancy (n=4), day 12 cyclic controls (n=5), day 15 cyclic controls (n=3), day 18 cyclic controls (n=4). Study II: Treatment with human interferon alpha (IFNA); IFNA treatment group (IFNA, n=3 heifers), placebo group (PLAC, n=3 heifers), control group (CONT, n=3 heifers).
2011-10-31 | E-GEOD-30694 | biostudies-arrayexpress
Project description:Chronic hepatitis C virus (HCV) infection is now routinely treated with interferon (IFN)-free regimens composed of directly acting antiviral (DAA) agents. Changes in hepatic and peripheral innate and adaptive immune function during DAA therapy associate with achieving a sustained virologic response (SVR). The present study explored the impact of cirrhosis on host endogenous interferon pathways during DAA therapy. mRNA and micro-RNA (miRNA) expression profiling was performed on paired pre- and end-of-treatment (EOT) liver biopsies from subjects treated with a 2 DAA regimen (sofosbuvir/ledipasvir [SOF/LDV]) for 12 weeks (n=4, 3 with cirrhosis) or a 3 DAA regimen (SOF/LDV with GS-9669 or GS-9451) for 6 weeks (n=6, 0 with cirrhosis). Nine of ten subjects achieved SVR, with one relapse in the GS-9669 treatment arm (ISHAK fibrosis 4). Hepatic interferon-stimulated gene expression was down-regulated in the liver of all subjects, with no observable impact of cirrhosis or duration of treatment. Hepatic down-regulation of all type-III IFNs was observed (IFNL1, IFNL2, IFNL3, IFNL4-ΔG), while IFNA2 expression, undetectable in all subjects pre-treatment, was detected in 3 of 9 subjects at EOT (all 3 achieved SVR). Only the subject who relapsed had detectable IFNL4-ΔG expression in EOT liver. No change in IFNB1, IFNG, or IFNA5 expression was observed, and expression of other type-I IFNs (IFNA1, IFNA4, IFNA5, IFNA6, IFNA8, IFNA16, IFNA17) was not detected pre- or post-treatment. While expression of multiple miRNAs changed in liver tissue over the course of treatment, most miRNAs previously associated with HCV replication, innate interferon signaling, and hepatic fibrosis did not change significantly. Conclusions: Changes in the host IFN-response during DAA therapy associate with favorable treatment outcome regardless of composition and duration of therapy or extent of hepatic fibrosis.
2017-02-09 | GSE70779 | GEO
Project description:To investigate effect of antisense oligonucleotides targeting the murine IFNa receptor (Ifnar1 ASOs) in a transgenic mouse model of cerebral interferonopathy (GIFN), mice were injected intracerebroventricularly with Ifnar1 ASOs. We performed DGE-Seq on brain cortex samples to determine the impact of ASOs on the transcriptome. Treatment of GIFN mice with Ifnar1 ASOs resulted in a significant decrease in Interferon gene expression and dampened the hyperinflammatory transcriptomic landscape in the brains of GIFN mice.
2023-12-22 | GSE231627 | GEO
Project description:We analyze the expression profile of ISGs in the context of IFNAR1-KO primary murine B cells and macrophages. These analses were used to define ISG gene sets that are under tonic control. Furthermore, these analyses enabled the definition of ISGs that are dependent on Tyk2 signaling. Male C57BL/6 IFNAR1-KO mice were injected subcutaneously with 10,000U IFNa for 2hrs. Splenic B cells and peritoneal macrophages were sorted by FACS directly into TriZol and gene expression profiling was performed on Affymetrix Mouse Gene 1.0 ST Arrays.
2015-11-20 | E-GEOD-75203 | biostudies-arrayexpress
Project description:Interferon tau (IFNT), a Type I IFN similar to alpha IFNs (IFNA), is the pregnancy recognition signal, produced by the ruminant conceptus. To elucidate specific effects of bovine IFNT and of other conceptus-derived factors, endometrial gene expression changes during early pregnancy were compared to gene expression changes after intrauterine application of human IFNA2. In study one, endometrial tissue samples were obtained on days (D) 12, 15, and 18 post-mating from nonpregnant or pregnant heifers. In study two, heifers were treated from D14 to D16 of the estrous cycle with an intrauterine device releasing IFNA2 or placebo lipid extrudates or PBS only as controls. Endometrial biopsies were collected after flushing the uterus. All samples from both experiments were analyzed with an Affymetrix Bovine Genome Array. Study one revealed differential gene expression between pregnant and nonpregnant endometria on D15 and D18. In study two, IFNA2 treatment resulted in differential gene expression in the bovine endometrium. Comparison of the datasets from both studies identified genes that were differentially expressed in response to IFNA2 but not in response to pregnancy on D15 or D18. Vice versa, genes were found as differentially expressed during pregnancy but not after IFNA2 treatment. In study three, spatiotemporal alterations in expression of selected genes were determined in uteri from nonpregnant and early pregnant heifers using in situ hybridization. The findings of this study suggest differential effects of bovine IFNT compared to human IFNA2 and that some pregnancy-specific changes in the endometrium are elicited by conceptus-derived factors other than IFNT.
2011-10-31 | GSE30694 | GEO
Project description:BMDMs or iMACs were generated via differentiation of bone marrow cells or immortalized precursors, respectively, in culture media containing m-CSF for 7 day. Upon differentiation, BMDMs or iMacs were left untreated or stimulated as described below. 1) BMDM WT were stimulated with IFNa, LPS, PGE2, IL-4, IL-10, LPS+PGE2, LPS+IL-4, LPS+IL-10, IFNa+PGE2, IFNa+IL-10: each condition in duplicate. This experiment was performed to investigate transcriptional cross-antagonism in the concomitant presence of pro-inflammatory (LPS or IFNa) and anti-inflammatory stimuli (IL-4, IL-10, or PGE2). 2) BMDM WT were stimulated with LPS, in the presence or absence of PFI-1 (Brd2/4 inhibitor) or SGC-CBP30 (CBP/p300 inhibitor): each condition in triplicate. This experiment was performed to define pro-inflammatory genes dependent or not on chromatin remodeling for their induction. 3) BMDM Mef2C/D proficient (Vav-Cre) or BMDM Mef2C/D KO (obtained by crossing Mef2d-/- Mef2cfl/fl with Vav-Cre mice) were stimulated with LPS, PGE2, or LPS+PGE2: each condition in triplicate. This experiment was performed to investigate the role of MEF2C-D on LPS transcritptional response. 4) BMDM WT were pretreated for 40 minutes with an anti-IL10R antibody or the corresponding isotope control, and then left untreated or stimulated with LPS, PGE2 or LPS+PGE2: each condition in duplicate. This experiment was performed to investigate the crosstalk between IL-10 and PGE2. 5) BMDM WT were left untreated or stimulated with PGE2, LPS, LPS+PGE2, or LPS+PGE2+IFNb. In the latter condition, IFNb was added 1 hour after the beginning of the costimulation: each condition in triplicate. This experiment was performed to asses the impact of PGE2 into the LPS-mediated IFNb induction. 5) MEF2A-deficient iMac clones (D7, A7, A8, C7) and MEF2A-proficient (referred to as wild-type) iMac clones (NE, B3 and D10) were generated via CRISPR/Cas9 and stimulated or not with LPS: each condition in single. This experiment was performed to investigate the role of MEF2A on LPS transcritptional response.
2021-06-08 | E-MTAB-9275 | biostudies-arrayexpress
Project description:IFNb has been used as a first line therapy for relapsing remitting multiple sclerosis (RRMS). Since only a few studies have addressed the role of endogenous IFNb in the pathogenesis of the disease, our objective was to characterize its role in the transcriptional regulation of pathogenic Th17 cytokines in patients with RRMS. In-vitro studies have demonstrated that IFNb inhibited IL-17A, IL-17F, IL-21, IL-22 and IFN-b secretion in CD4+ lymphocytes through the induction of suppressor of cytokine secretion (SOCS)1 and 3. We found that patients with RRMS have increased serum and cerebrospinal fluid (CSF) Th17 (IL-17A and IL-17F) cytokine levels in comparison to the control subjects, suggesting that deficient endogenous IFNbeta secretion and/or signaling may contribute to the dysregulation of those pathogenic cytokines in CD4+ cells. We identified that the endogenous IFNb from serum of RRMS patients induced a significantly lower IFN-inducible gene expression in comparison to healthy controls (HCs). In addition, in-vitro studies have revealed a deficient endogenous and exogenous IFNb signaling in CD4+ cells derived from MS patients. Interestingly, upon inhibition of the endogenous IFNb signaling by silencing interferon regulatory factor (IRF)7 gene expression, the resting CD4+ T cells secreted significantly higher level of IL-17A, IL-17F, IL-21, IL-22 and IL-9, suggesting that endogenous IFNb suppresses the secretion of these pathogenic cytokines. In-vivo recombinant IFNb-1a treatment induced IFNAR1 and its downstream signaling molecules’ gene expression, suggesting that treatment may reconstitute a deficient endogenous IFNbeta regulation of the CD4+ T-cells’ pathogenic cytokine production in MS patients.
2014-05-15 | GSE53716 | GEO
Project description:IFNα-mediated gene expression pattern. Direct effects of IFNα on human CD8 T cells without any other concomitant signal. This analysis examined the direct effects of IFNa on human CD8 T cells without any other concomitant signal. Total human CD8 T cells were magnetically sorted from peripheral blood by negative selection. In order to minimize the presence of antigen-experienced cells, total human CD8 T cells were depleted of CD45RO+ cells by labelling with anti-CD45RO magnetic bead. In both steps of cellular sorting, negative selection were preferred to positive selection to avoid direct labelling of CD8 T cell surface molecules could interfere with downstream IFNa-mediated signalling. Magnetically sorted untouched human CD8+CD45R0- T cells from three different donors were unstimulated or stimulated with IFNa2b or IFNa5 and cells were harvested 7 hours later. mRNAs from the 3 subjects were pooled and analyzed using Affymetrix human HG-U133A 2.0 array gene chips Fold-change ≥ 2 criterion was used to identify genes which expression differed between treatment and control (unstimulated cells). Keywords: Gene expression pattern analysis Magnetically sorted untouched CD8+CD45R0-T cells mRNA pooled sample from three different donors unstimulated or stimulated with IFN alfa 2b or IFN alfa 5 for 7 hours.
2010-07-23 | E-GEOD-17299 | biostudies-arrayexpress