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Multi-omics approaches reveal TNF-mediated inhibition of tissue reparative macrophages is via a gene-selective transcriptional mechanism

ABSTRACT: Anti-TNF therapies are a core anti-inflammatory approach for chronic diseases such as rheumatoid arthritis and Crohn’s Disease. Previously, we and others found that TNF blocks the emergence and function of alternatively-activated or M2 macrophages involved in wound healing and tissue-reparative functions. Conceivably, anti-TNF drugs could mediate their protective effects in part by an altered balanced of macrophage activity. To understand the mechanistic basis of how TNF regulates tissue-reparative macrophages we used RNAseq, scRNAseq, ATACseq, time-resolved phospho-proteomics, gene-specific approaches, metabolic analysis and signaling pathway deconvolution. Our findings reveal that TNF controls tissue-reparative macrophage gene expression in a highly gene-specific way dependent on JNK signaling. We uncover principles of the selectively inhibition by TNF via the type 1 TNF receptor on specific populations of alternative activated macrophages.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Macrophage

SUBMITTER: Mario Oroshi

LAB HEAD: Peter Murray

PROVIDER: PXD028667 | Pride | 2022-01-07

REPOSITORIES: Pride

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Multi-omics approaches reveal TNF-mediated inhibition of tissue reparative macrophages is via a gene-selective transcriptional mechanism (ATAC-Seq)

Project description:Anti-TNF therapies are a core anti-inflammatory approach for chronic diseases such as rheumatoid arthritis and Crohn’s Disease. Previously, we and others found that TNF blocks the emergence and function of alternatively-activated or M2 macrophages involved in wound healing and tissue-reparative functions. Conceivably, anti-TNF drugs could mediate their protective effects in part by an altered balanced of macrophage activity. To understand the mechanistic basis of how TNF regulates tissue-reparative macrophages we used RNAseq, scRNAseq, ATACseq, time-resolved phospho-proteomics, gene-specific approaches, metabolic analysis and signaling pathway deconvolution. Our findings reveal that TNF controls tissue-reparative macrophage gene expression in a highly gene-specific way dependent on JNK signaling. We uncover principles of the selectively inhibition by TNF via the type 1 TNF receptor on specific populations of alternative activated macrophages.

2022-01-11 | GSE185375 | GEO

Multi-omics approaches reveal TNF-mediated inhibition of tissue reparative macrophages is via a gene-selective transcriptional mechanism (scRNA-Seq)

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Multi-omics approaches reveal TNF-mediated inhibition of tissue reparative macrophages is via a gene-selective transcriptional mechanism (bulk RNA-Seq)

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2021-10-11 | PXD021366 | Pride

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Self-maintenance of Cardiac Resident Reparative Macrophages Attenuates Doxorubicin-induced Cardiomyopathy through the SR-A1-c-Myc Axis

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2019-04-03 | GSE129225 | GEO

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TNF promotes SREBP activity to regulate macrophage polarization and tissue repair [ATAC-seq]

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