Memory-like HCV-specific CD8+ T cells retain a molecular scar after cure of chronic HCV infection
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ABSTRACT:
PROVIDER: PRJNA631795 | ENA |
REPOSITORIES: ENA
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Project description:Memory-like HCV-specific CD8+ T cells retain a chronic scar after cure of chronic HCV infection
| PRJNA631746 | ENA
Project description:Investigation of phenotypical changes between exhausted HCV-specific CD8+ T cells during chronic infection and after DAA-mediated cure investigation of heterogeneity withhin the HCV-specific CD8+ T cell population
2020-09-07 | GSE150345 | GEO
Project description:Investigation of phenotypical changes between exhausted HCV-specific CD8+ T cells during chronic infection and after DAA-mediated cure investigation of heterogeneity withhin the HCV-specific CD8+ T cell population
2020-09-08 | GSE150305 | GEO
Project description:Chronic hepatitis C virus (HCV) infection is associated with CD8+ T-cell exhaustion characterized by limited effector functions and thus compromised anti-viral activity. Exhausted HCV-specific CD8+ T cells are comprised of memory-like and terminally exhausted CD8+ T-cell subsets. So far, little is not known about the molecular profile and fate of these cells after elimination of chronic antigen stimulation by direct acting antiviral therapy (DAA). Here, we report an antigen-driven molecular core signature underlying exhausted CD8+ T-cell subset heterogeneity in chronic viral infection with a progenitor/progeny relationship of memory-like and terminally exhausted HCV-specific CD8+ T cells via an intermediate stage. Furthermore, transcriptional profiling reveals that the memory-like cells remain after DAA-mediated cure while terminally exhausted HCV-specific CD8+ T-cell subsets are lost. Thus, the memory polarization of the overall HCV-specific CD8+ T-cell response after cure does not result from re-differentiation of exhausted T cells. Consequently, antigen elimination has little impact on the exhausted core signature of memory-like CD8+ T cells that remains clearly different from bona fide T-cell memory. These results identify a molecular signature of T-cell exhaustion that is imprinted like a chronic scar in HCV-specific CD8+ T cells even after HCV cure, highlighting the requirement of re-programming to elicit full effector potential of exhausted T cells.
| EGAS00001004538 | EGA
Project description:Although treatment of chronic hepatitis C virus (HCV) infection with direct acting antivirals (DAAs) results in high rates of cure, liver fibrosis does not resolve immediately after HCV eradication. Resolution of fibrosis occurs in some, but not all patients, after HCV cure, and hepatic decompensation and hepatocellular carcinoma can still occur in patients with pre-existing cirrhosis. We hypothesized that evaluation of the host liver proteome in the context of HCV treatment would provide insight into how inflammatory and fibrinogenic pathways change upon HCV eradication. We evaluated the whole liver proteome and phosphoproteome using paired liver biopsies from 8 HCV-infected patients collected before or immediately after treatment with DAAs in clinical trials. We identify interferon stimulated proteins as the predominant pathways that decrease with HCV treatment, which is consistent with previous analyses of the liver transcriptome during DAA therapy. While there was no change in the proteome of pathways associated with liver fibrosis, we identified a decrease in the phosphoproteome signature for ERK1/ERK2 as a result of HCV treatment. Conclusion: There is a reduction in the endogenous interferon-mediated antiviral response and alterations in the phosphoproteome that may precede resolution of fibrosis in the liver immediately after treatment of HCV with DAAs.
2023-03-11 | PXD024846 | Pride
Project description:Chronic hepatitis C virus (HCV) infection is associated with CD8+ T-cell exhaustion characterized by limited effector functions and thus compromised anti-viral activity. Exhausted HCV-specific CD8+ T cells are comprised of memory-like and terminally exhausted CD8+ T-cell subsets. So far, little is not known about the molecular profile and fate of these cells after elimination of chronic antigen stimulation by direct acting antiviral therapy (DAA). Here, we report an antigen-driven molecular core signature underlying exhausted CD8+ T-cell subset heterogeneity in chronic viral infection with a progenitor/progeny relationship of memory-like and terminally exhausted HCV-specific CD8+ T cells via an intermediate stage. Furthermore, transcriptional profiling reveals that the memory-like cells remain after DAA-mediated cure while terminally exhausted HCV-specific CD8+ T-cell subsets are lost. Thus, the memory polarization of the overall HCV-specific CD8+ T-cell response after cure does not result from re-differentiation of exhausted T cells. Consequently, antigen elimination has little impact on the exhausted core signature of memory-like CD8+ T cells that remains clearly different from bona fide T-cell memory. These results identify a molecular signature of T-cell exhaustion that is imprinted like a chronic scar in HCV-specific CD8+ T cells even after HCV cure, highlighting the requirement of re-programming to elicit full effector potential of exhausted T cells.
| EGAD00001006259 | EGA
Project description:Transcriptionnal analysis of pathogenic IgM Memory B cells stimulated or not with CpG from 3 differents HCV related Cryoglobulinemia.
2019-07-11 | GSE114357 | GEO
Project description:Dipeptidyl peptidase 4 (Dpp4) plays a pivotal role in fibrotic and nonfunctional scar development following skin injury and is present in a subset of fibroblasts implicated in scar formation. Simultaneously, heterogeneous vascular endothelial cells (ECs) retain their capacity to drive tissue regeneration and repair within scarred areas. Effective strategies for inhibiting scar-associated fibroblasts and regulating EC subtypes in the scar microenvironment remain unclear. Here, we engineered CAR-Trem2-Ms capable of targeting DPP4+ fibroblasts and modulating EC phenotypes within the scar microenvironment to effectively prevent and treat scarring. Furthermore, compared to those in normal control samples, DPP4 expression levels were higher in both clinical scar databases and samples from scar patients. We transferred a CAR gene specifically targeting Dpp4+ fibroblasts into macrophages, which were then induced into CAR-Trem2-Ms with 1,25-dihydroxycholecalciferol (an active form of VD, VD3). Hydrogel micropore micro
2024-09-24 | GSE248960 | GEO
Project description:Dipeptidyl peptidase 4 (Dpp4) plays a pivotal role in fibrotic and nonfunctional scar development following skin injury and is present in a subset of fibroblasts implicated in scar formation. Simultaneously, heterogeneous vascular endothelial cells (ECs) retain their capacity to drive tissue regeneration and repair within scarred areas. Effective strategies for inhibiting scar-associated fibroblasts and regulating EC subtypes in the scar microenvironment remain unclear. Here, we engineered CAR-Trem2-Ms capable of targeting DPP4+ fibroblasts and modulating EC phenotypes within the scar microenvironment to effectively prevent and treat scarring. Furthermore, compared to those in normal control samples, DPP4 expression levels were higher in both clinical scar databases and samples from scar patients. We transferred a CAR gene specifically targeting Dpp4+ fibroblasts into macrophages, which were then induced into CAR-Trem2-Ms with 1,25-dihydroxycholecalciferol (an active form of VD, VD3). Hydrogel micropore microneedles (mMNs) were employed to deliver CAR-Trem2-Ms to effectively alleviate scar formation. Single-cell transcriptome sequencing and analysis revealed that CAR-Trem2-Ms could modify EC phenotypes and regulate fibrosis by suppressing the profibrotic gene Lrg1. CAR-Trem2-Ms effectively inhibited fibrosis in fibroblasts induced by high EC LRG1 expression in vitro, further revealing the underlying mechanism by which CAR-Trem2-Ms exert their antifibrotic effects. Our findings offer a promising approach for treating post-traumatic scarring and provide novel insights into the pathological mechanisms underlying fibrosis.
2024-09-24 | GSE248759 | GEO
Project description:Hepatic complications of HCV infection, including fibrosis and cirrhosis are accelerated in HIV-infected individuals. Although liver biopsy remains the gold standard for staging HCV-associated liver disease, this test can result in serious complications and is subject to sampling error. These challenges have prompted a search for non-invasive methods for liver fibrosis staging. To this end, we compared serum proteome profiles at different stages of fibrosis in HIV/HCV co- and HCV mono-infected patients using SELDI-TOF MS.
2018-04-09 | PXD009007 | Pride