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Baricitinib attenuates the proinflammatory phase1 of COVID-19 driven by lung-infiltrating monocytes

ABSTRACT: Baricitinib attenuates the proinflammatory phase1 of COVID-19 driven by lung-infiltrating monocytes

PROVIDER: PRJNA773942 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR16549300.fastq.gz	Fastqsanger.gz
	SRR16549301.fastq.gz	Fastqsanger.gz
	SRR16549302.fastq.gz	Fastqsanger.gz
	SRR16549303.fastq.gz	Fastqsanger.gz
	SRR16549304.fastq.gz	Fastqsanger.gz

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Baricitinib attenuates the proinflammatory phase1 of COVID-19 driven by lung-infiltrating monocytes

Project description:COVID-19 patients are generally asymptomatic during initial SARS-CoV-2 replication, but may suffer severe immunopathology after the virus has receded and blood monocytes have infiltrated the airways. In the bronchoalveolar lavage fluid from patients with severe COVID-19, lung-infiltrating monocytes expressed high mRNA levels encoding inflammatory mediators, including CXCL8and IL-1ß, and contained SARS-CoV-2transcripts. To study this process in more depth, we developed a novel organotypic model whereby primary human blood monocytes are transmigrated across a differentiated human lung epithelium infected by SARS-CoV-2. Infiltrating monocytes acquiredSARS-CoV-2 from the epithelium and upregulated expression and secretion of inflammatory mediators includingCXCL8 and IL-1ß, mirroring in vivo data. The JAK1/2inhibitor baricitinib gained emergency use authorization by the FDA for the treatment of COVID-19 originally in combination with the antiviral remdesivir, and recently as a stand-alone treatment. To explore the mechanisms by which baricitinib alone or in combination with remdesivir may result in more favorable disease outcomes, we leveraged this model to characterize viral burden, gene expression and inflammatory mediator secretion by lung epithelial cells and infiltrating monocytes. As expected, remdesivir decreased viral burden in both the epithelium and monocytes, while baricitinib enhanced antiviral signaling and decreased specific inflammatory mediators in monocytes. Combined use of baricitinib and remdesivir enhanced the rate of virus clearance from SARS-CoV-2-positivemonocytes. Taken together, baricitinib enhances the antiviral state of monocytes infiltrating the COVID-19 lung, while decreasing the expression of inflammatory mediators, thus limiting the likelihood of a cytokine storm and ensuing acute respiratory distress syndrome (ARDS).

2021-10-30 | GSE186460 | GEO

Baricitinib attenuates the proinflammatory phase of COVID-19 driven by lung-infiltrating monocytes.

Project description:SARS-CoV-2-infected subjects are generally asymptomatic during initial viral replication but may suffer severe immunopathology after the virus has receded and monocytes have infiltrated the airways. In bronchoalveolar lavage fluid from severe COVID-19 patients, monocytes express mRNA encoding inflammatory mediators and contain SARS-CoV-2 transcripts. We leverage a human small airway model of infection and inflammation, whereby primary blood monocytes transmigrate across SARS-CoV-2-infected lung epithelium to characterize viral burden, gene expression, and inflammatory mediator secretion by epithelial cells and monocytes. In this model, lung-infiltrating monocytes acquire SARS-CoV-2 from the epithelium and upregulate expression and secretion of inflammatory mediators, mirroring in vivo data. Combined use of baricitinib (Janus kinase inhibitor) and remdesivir (nucleoside analog) enhances antiviral signaling and viral clearance by SARS-CoV-2-positive monocytes while decreasing secretion of proneutrophilic mediators associated with acute respiratory distress syndrome. These findings highlight the role of lung-infiltrating monocytes in COVID-19 pathogenesis and their importance as a therapeutic target.

| S-EPMC9130711 | biostudies-literature

Expression data from infiltrating monocytes into lungs

Project description:Expression data from infiltrating monocytes into lungs

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Gene expression profile of healthy-donor peripheral monocytes, glioblastoma-patient peripheral monocytes, and glioblastoma-infiltrating myeloid cells

Project description:We compared gene expression profile between healthy-donor peripheral monocytes and glioblastoma-patient peripheral monocytes as well as glioblastoma-patient peripheral monocytes with matched tumor-infiltrating myeloid cells.

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2023-10-25 | GSE216515 | GEO

Tumor-infiltrating CCR2+ inflammatory monocytes counteract specific immunotherapy

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2014-09-23 | E-GEOD-51332 | biostudies-arrayexpress

Treatment of C3H/HeJ grafted mice with baricitinib [prevention]

Project description:The C3H/HeJ grafted model of alopecia areata was used to determine the efficacy of systemic baricitinib at preventing alopecia or treating established disease. The efficacy of topical baricitinib at treating established alopecia in the C3H/HeJ grafted model was also assessed. Microarrays were performed on skin RNA at week 0 and week 12 after starting treatment in all models. Baricitinib was administered in systemic form at the time of grafting. Skin samples were taken after 12 weeks.

2015-05-01 | E-GEOD-61551 | biostudies-arrayexpress

Treatment of C3H/HeJ grafted mice with baricitinib [systemic]

Project description:The C3H/HeJ grafted model of alopecia areata was used to determine the efficacy of systemic baricitinib at preventing alopecia or treating established disease. The efficacy of topical baricitinib at treating established alopecia in the C3H/HeJ grafted model was also assessed. Microarrays were performed on skin RNA at week 0 and week 12 after starting treatment in all models. Baricitinib was administered in systemic form after disease establishment. Skin samples were taken at the start of treatment and after 12 weeks.

2015-05-01 | E-GEOD-61552 | biostudies-arrayexpress

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