Identification of Novel Genetic Regulatory Region for Proprotein Convertase FURIN and Interferon Gamma in T Cells

Ortutay, Zsuzsanna; Grönholm, Anna; Laitinen, Melina; Keresztes-Andrei, Melinda; Hermelo, Ismaïl; Pesu, Marko

doi:10.3389/fimmu.2021.630389

Cited by 8 publications

(9 citation statements)

References 94 publications

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“…4D ). These included upregulation of LAG3 on Cytotoxic γδ T cells and increased expression of inflammatory regulators OTULIN ( 79 ) and FURIN ( 80 ) on Inflammatory γδ T cells. Within Type 3 and Naive γδ T cells, upregulated genes included those related to inflammatory regulation ( TMSB10; which suppresses inflammatory macrophages)( 81 ), HIF1A; which controls γδ T cell mediated inflammation( 82 ) and BATF; which is upregulated in exhausted CD8 T cells ( 83 )), cell exhaustion ( PDCD1 (encoding PD1); which dampens inflammatory and cytotoxic potential of γδ T cell ( 84, 85 ), TNFRSF4 (encoding OX40) and HAVCR2 (encoding Tim-3); which reduces cytokine and cytotoxic potential of γδ T cells ( 86 ) and pro-apoptotic signalling ( TXNIP ).…”

Section: Resultsmentioning

confidence: 99%

Malaria drives unique regulatory responses across multiple immune cell subsets

Dooley

Chabikwa

Pava

et al. 2022

Preprint

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Plasmodium falciparum malaria results in immunoregulatory responses across multiple cell subsets, which protects the individual from inflammatory mediated immunopathogenesis. However, these anti-inflammatory responses also hamper the development of effective anti-parasitic immunity. Understanding malaria induced tolerogenic responses in specific cell subsets may inform the development of strategies to boost protective immunity during drug treatment and vaccination. Here, we analysed the immune landscape with single cell RNA sequencing of peripheral blood mononuclear cells during falciparum malaria and at convalescence in children and adults from a low malaria transmission area in Malaysia. To understand malaria driven changes specific to each immune cell subset, we interrogated transcriptional changes in sub-clustered major immune cell types during infection. We found that malaria drove development of immunosuppressive monocytes, alongside NK and γδ T cells which regulated inflammatory function but maintained cytolytic capacity. IL10-producing CD4 T cells and IL10-producing regulatory B cells were also induced. Type I interferon responses were identified across all cell types, linking Type I interferon signalling with the induction of immunoregulatory networks during malaria. Together, these findings provide insights into cell-specific and shared immunoregulatory changes induced during malaria, and provides a data set resource for additional analysis of anti-parasitic immunity and disease pathogenesis.

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Section: Resultsmentioning

confidence: 99%

Malaria drives unique regulatory responses across multiple immune cell subsets

Dooley

Chabikwa

Pava

et al. 2022

Preprint

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“…Other SARS-CoV-2 entry-associated factors are subject to epigenetic regulation as well. A recent study identified a regulatory region upstream of FURIN gene that is heavily occupied by the histone acetyltransferase p300 in T cells [87]. Also, DNMT1-mediated hypermethylation of TMPRSS2 was associated with its downregulation [88].…”

Section: Regulation Of Sars-cov-2 Entry-associated Factors By Epigenetic Mechanismsmentioning

confidence: 99%

Epigenetic Regulation Mechanisms in Viral Infections: A Special Focus on COVID-19

Süt¹

2022

Biotechnology to Combat COVID-19

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The outbreak of Coronavirus Disease-2019 (Covid-19), caused by a novel and highly pathogenic coronavirus (severe acute respiratory syndrome coronavirus-2, SARS-CoV-2), is a persisting global health concern. Research so far has successfully identified the molecular mechanisms of viral entry, alterations within the host cell upon infection, and the stimulation of an immune response to fight it. One of the most important cellular regulatory machineries within the host cell to be affected by the SARS-CoV-2 infection is epigenetic regulation, which modulates transcriptional activity by DNA sequence-independent factors such as DNA-methylation, RNA interference and histone modifications. Several studies in the literature have previously reported epigenetic alterations within the host due to infections of the Coronaviridae family viruses including SARS-CoV and MERS-CoV that antagonized immune system activation. Recent studies have also identified epigenetic dysregulation of host metabolism by SARS-CoV-2 infection, linking epigenetic mechanisms with the pathophysiology and illness severity of Covid-19. Therefore, this book chapter aims to provide a comprehensive overview of the epigenetic regulation mechanisms in viral infections with a special focus on SARS-CoV-2 infection.

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Section: Furin and Its Inhibitorsmentioning

confidence: 99%

“…Furin is a serine protease that belongs to the proprotein convertase subtilisin kexin (PCSK) family [108,109]. This protease is expressed everywhere in organs and tissues, such as the gastrointestinal tract, lung, central nervous system, and reproductive tissues [109]. Furin plays a prominent role in viral pathogenesis in all cells and efficiently cleaves polybasic or multibasic sites identified in the influenza virus (e.g., influenza virus subtypes H5 and H7).…”

Section: Furin and Its Inhibitorsmentioning

confidence: 99%

Host Cell Proteases Mediating SARS-CoV-2 Entry: An Overview

Oubahmane

Hdoufane

Bjij

et al. 2022

CTMC

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The outbreak of the SARS-CoV-2 virus in late 2019 and the spread of the COVID-19 pandemic have caused severe health and socioeconomic damage worldwide. Despite the significant research effort to develop vaccines, antiviral treatments, and repurposed therapeutics to effectively contain the catastrophe, there are no available effective vaccines or antiviral drugs that are able to limit the threat of the disease, so the infections continue to expand. To date, the search for effective treatment remains a global challenge. Therefore, it is imperative to develop therapeutic strategies to contain the spread of SARS-CoV-2. Like other coronaviruses, SARS-CoV-2 invades and infects human host cells via the attachment of its spike envelope glycoprotein to the human host cell receptor hACE2. Subsequently, several host cell proteases facilitate viral entry via proteolytic cleavage and activation of the S protein. These host cell proteases include, type II transmembrane serine proteases (TTSPs), cysteine cathepsins B and L, furin, trypsin, and Factor Xa among others. Given the critical role of the host cell proteases in coronavirus pathogenesis, their inhibition by small molecules has successfully targeted SARS-CoV-2 in vitro, suggesting that host cell proteases are attractive therapeutic targets for SARS-CoV-2 infection. In this review, we focus on the biochemical properties of host cell proteases that facilitate the entry of SARS-CoV-2, and we highlighted therapeutic small molecule candidates that have been proposed through in silico research.

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Identification of Novel Genetic Regulatory Region for Proprotein Convertase FURIN and Interferon Gamma in T Cells

Cited by 8 publications

References 94 publications

Malaria drives unique regulatory responses across multiple immune cell subsets

Malaria drives unique regulatory responses across multiple immune cell subsets

Epigenetic Regulation Mechanisms in Viral Infections: A Special Focus on COVID-19

Host Cell Proteases Mediating SARS-CoV-2 Entry: An Overview

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