Complete TLR3 deficiency
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE30951 | GEO | 2011/11/02
SECONDARY ACCESSION(S): PRJNA146247
REPOSITORIES: GEO
Similar Datasets
Project description:The objective of this study is to study the Toll-like receptor 3 (TLR3)-dependent gene expression in human fibroblast cells and peripheral blood mononuclear cells (PBMCs) Fibroblast cells and PBMCs from donors with autosomal recessive (AR) complete TLR3 deficiency and autosomal dominant (AD) partial TLR3 deficiency were collected for microarray analysis to measure the transcriptional responsiveness of TLR3 in fibroblast and PBMCs. A total of 3 healthy controls, 1 AD TLR3-deficient patient, 1 AR TLR3-deficient patient, 1 AR UNC-93B-deficient patient, 1 MyD88 deficient patien were used in this study. The fibroblast cells were cultured in DMEM medium supplemented with 10% fetal calf serum (FCS). The PBMCs were cultured in RPMI medium complemented with 10% FCS. Different kinetics (2 hours and 8 hours) of poly(I:C) (25ug/ml, purchased from Amersham) stimulations were performed, aiming to define TLR3-inducible genes in these human cells. A stimulation of IL-1β (20ng/ml, purchased from R&D system Inc.) was used as a positive activation control with same kinetics of stimulations. A total of one million cells per stimulation were used for fibroblasts, and around 1.5 million cells per stimulation for PBMCs.
2011-11-02 | E-GEOD-30951 | biostudies-arrayexpress
Project description:Hepatitis C virus (HCV) is the most common chronic blood-borne infection in the United States with the majority of patients becoming chronically infected and a subset (20%) progressing to cirrhosis and hepatocellular carcinoma. Individual variations in immune responses may help define successful resistance to infection with HCV. We have examined the immune response in primary macrophages from patients who have spontaneously cleared HCV (viral load negative, VL-, n = 37) compared to HCV genotype 1 chronically infected (VL+) subjects (n=32) and found that macrophages from VL- subjects have an elevated baseline expression of Toll-like receptor 3 (TLR3). Macrophages from HCV patients were stimulated ex vivo through the TLR3 pathway and assessed using gene expression arrays and pathway analysis. We found elevated TLR3 response genes and pathway activity from VL- subjects. Furthermore, macrophages from VL- subjects showed higher production of IFN-b and related IFN response genes by Q-PCR, and increased phosphorylation of STAT-1 by immunoblot. Analysis of polymorphisms in TLR3 revealed a significant association of intronic TLR3 polymorphism (rs13126816) with the clearance of HCV and the expression of TLR3. Of note, PBMCs from the same donors showed opposite changes in gene expression, suggesting ongoing inflammatory responses in PBMCs from VL+ HCV patients. Our results suggest that an elevated innate immune response enhances HCV clearance mechanisms and may offer a potential therapeutic approach to increase viral clearance. Differential gene expression by primary human macrophages and PBMCs from patients with spontaneous clearance of HCV (VL-) and patients with chronic HCV infection (VL+) were generated by microarray.
2013-03-05 | E-GEOD-40812 | biostudies-arrayexpress
Project description:Hepatitis C virus (HCV) is the most common chronic blood-borne infection in the United States with the majority of patients becoming chronically infected and a subset (20%) progressing to cirrhosis and hepatocellular carcinoma. Individual variations in immune responses may help define successful resistance to infection with HCV. We have examined the immune response in primary macrophages from patients who have spontaneously cleared HCV (viral load negative, VL-, n = 37) compared to HCV genotype 1 chronically infected (VL+) subjects (n=32) and found that macrophages from VL- subjects have an elevated baseline expression of Toll-like receptor 3 (TLR3). Macrophages from HCV patients were stimulated ex vivo through the TLR3 pathway and assessed using gene expression arrays and pathway analysis. We found elevated TLR3 response genes and pathway activity from VL- subjects. Furthermore, macrophages from VL- subjects showed higher production of IFN-b and related IFN response genes by Q-PCR, and increased phosphorylation of STAT-1 by immunoblot. Analysis of polymorphisms in TLR3 revealed a significant association of intronic TLR3 polymorphism (rs13126816) with the clearance of HCV and the expression of TLR3. Of note, PBMCs from the same donors showed opposite changes in gene expression, suggesting ongoing inflammatory responses in PBMCs from VL+ HCV patients. Our results suggest that an elevated innate immune response enhances HCV clearance mechanisms and may offer a potential therapeutic approach to increase viral clearance.
2013-03-05 | GSE40812 | GEO
Project description:We report here two unrelated HSE patients carrying different heterozygous mutations (D50A and G159A) in TBK1, the gene encoding TANK-binding kinase 1, a kinase at the crossroads of multiple IFN-inducing signaling pathways. Both mutant TBK1 alleles are loss-of-function, but through different mechanisms: protein instability (D50A) or a loss of kinase activity (G159A). Both are also associated with an autosomal dominant (AD) trait, but by different mechanisms: haplotype-insufficiency (D50A) or negative dominance (G159A). A defect in poly(I:C)-induced TLR3 responses can be detected in fibroblasts heterozygous for G159A, but not for D50A TBK1. Skin fibroblast cell lines were derived from healthy controls (n=3), patients with deficiencies for TBK1 (n=2), TLR3 (n=2), STAT1 (n=1) and cultured for 2 or 8 hours in the presence of IFNa (105 IU/ml), IL1b (20ng/ml), or poly I:C (25ug/ml) or left unstimulated for the same length of time.
2012-07-29 | E-GEOD-38652 | biostudies-arrayexpress
Project description:In this study, we sequenced RNAs localized in the early endosome and lysosome and TLR3-binding RNAs, and identified Rmrp as a TLR3 binding early endosomal lncRNA. Further we investigated the biological funtion of Rmrp in vitro and in vivo, proving that Rmrp posivitely regulated TLR3 activation by inducing TLR3 dimerization. Cryo-EM structure of Rmrp-C-mTLR3-ECD complex further proved our conclusion.
2025-04-01 | GSE159459 | GEO
Project description:we assessed the impact of TLR3 L412F at endogenous cellular levels upon double stranded RNA (dsRNA) stimulation, by performing RNA-sequencing in primary fibroblasts from individuals homozygous for the ancestral allele (n =2) or homozygous for TLR3 L412F (n = 4) upon extracellular Poly(I:C) stimulation that activates the TLR3 pathway. The average response of TLR3 L412F homozygotes was significantly decreased (mean Δ log2 fold-change = 0.93; Wilcoxon p <10-16) compared to that of cells with the ancestral allele, approaching that of TLR3-deficient cells, used as negative control.
2023-01-13 | GSE216304 | GEO
Project description:We report here unrelated HSE patients with autosomal recessive (AR) or autosomal dominant (AD) TRIF deficiency. The AR form of the disease is due to a homozygous nonsense mutation, resulting in a complete absence of the TRIF protein. Both the TLR3 and the TRIF-dependent TLR4 signaling pathways are abolished. The AD form of TRIF deficiency is due to a heterozygous missense mutation resulting in a dysfunctional protein. The TLR3 signaling pathway is impaired, whereas the TRIF-dependent TLR4 pathway is unaffected. Both patients however showed reduced capacity to respond to cytosolic double stranded RNA, consistent with recent reports of TRIF’s involvement in the DExD/H-box helicases pathway. Skin fibroblast cell lines were derived from healthy controls (n=3), patient with deficiencies for TRIF (n=1), MYD88 (n=1), and TLR3 (n=1) and cultured for 4 hours in the presence of IL1B (20ng/ml) or poly I:C (25ng/ml) or left unstimulated for the same length of time. PBMCs (previously frozen) collected from a healthy control (n=1) and patients with deficiencies for TRIF (n=1), and MYD88 (n=1) were cultured together with LPS (10ng/ml) or R848 (3ug/ml) for 2hrs or left unstimulated for the same length of time.
2011-10-19 | E-GEOD-32390 | biostudies-arrayexpress
Project description:Endosomal lncRNA Rmrp is required for TLR3 innate sensing by engaging TLR3 dimerization
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Project description:Microarray was performed to comprehensively examine microRNA induction in murine small intestine after exposure to total body g-irradiation. Small intestines were collected from Tlr3+/+ and Tlr3-/- mice at 0 and 6 hr after exposure to 10 Gy of total body g-irradiation. Samples were pooled from 3 mice. Total RNA was extracted and subjected to microRNA microarray analysis.
2015-02-01 | E-GEOD-42916 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. How developmental programs reactivate in regeneration is a fundamental question in biology. We addressed this question through the study of Wound Induced Hair follicle Neogenesis (WIHN), an adult organogenesis model where stem cells regenerate de novo hair follicles following deep wounding. The exact mechanism is uncertain. Here we show that self-noncoding dsRNA activates the anti-viral receptor toll like receptor 3 (TLR3) to induce intrinsic retinoic acid (RA) synthesis in a pattern that predicts new hair follicle formation after wounding in mice. Additionally, in humans, rejuvenation lasers induce gene expression signatures for dsRNA and RA, with measurable increases in intrinsic RA synthesis. These results demonstrate a potent stimulus for RA synthesis by non-coding dsRNA, relevant to their broad functions in development and immunity.
2019-05-22 | GSE128868 | GEO