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An interferon gamma response signature links myocardial aging and immunosenescence

ABSTRACT: An interferon gamma response signature links myocardial aging and immunosenescence

PROVIDER: PRJNA896939 | ENA |

REPOSITORIES: ENA

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An interferon gamma response signature links myocardial aging and immunosenescence

Project description:Aging entails profound immunological transformations that can negatively impact the myocardial biology and predispose to myocardial diseases. However, preclinical research in the immune-cardiology field is mostly conducted in young healthy animals, which potentially weakens its translational relevance. Herein, we sought to investigate how the aging T-cell compartment impacts myocardial cell biology in elderly. By investigating the paired-wised age-related shifts in the heart and its draining lymph nodes, our study provides evidence for an increased myocardial IFN-gamma signaling, which is associated with inflammatory and metabolic shifts typically seen in heart failure (HF).

2023-03-10 | GSE217098 | GEO

An interferon gamma response signature links myocardial aging and immunosenescence.

Project description:AimsAging entails profound immunological transformations that can impact myocardial homeostasis and predispose to heart failure. However, preclinical research in the immune-cardiology field is mostly conducted in young healthy animals, which potentially weakens its translational relevance. Herein, we sought to investigate how the aging T-cell compartment associates with changes in myocardial cell biology in aged mice.Methods and resultsWe phenotyped the antigen-experienced effector/memory T cells purified from heart-draining lymph nodes of 2-, 6-, 12-, and 18-month-old C57BL/6J mice using single-cell RNA/T cell receptor (TCR) sequencing (sc-seq). Simultaneously, we profiled all non-cardiomyocyte cell subsets purified from 2- and 18-month-old hearts and integrated our data with publicly available cardiomyocyte sc-seq datasets. Some of these findings were confirmed at the protein level by flow cytometry. With aging, the heart-draining lymph node and myocardial T cells underwent clonal expansion and exhibited an up-regulated pro-inflammatory transcription signature, marked by an increased interferon-γ (IFN-γ) production. In parallel, all major myocardial cell populations showed increased IFN-γ responsive signature with aging. In the aged cardiomyocytes, a stronger IFN-γ response signature was paralleled by the dampening of expression levels of transcripts related to most metabolic pathways, especially oxidative phosphorylation. Likewise, induced pluripotent stem cells-derived cardiomyocytes (iPSC-CM) exposed to chronic, low grade IFN-γ treatment showed a similar inhibition of metabolic activity.ConclusionsBy investigating the paired age-related alterations in the T cells found in the heart and its draining lymph nodes, we provide evidence for increased myocardial IFN-γ signaling with age, which is associated with inflammatory and metabolic shifts typically seen in heart failure.

| S-EPMC10651211 | biostudies-literature

Long non-coding RNA GRASLND links melanoma differentiation and interferon-gamma response

Project description:Long non-coding RNA GRASLND links melanoma differentiation and interferon-gamma response

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RNA-seq of monocyte derived macrophages exposed to arachidonic acid, interferon beta, or interferon gamma

Project description:Monocyte derived macrophages were exposed to arachidonic acid, interferon beta, or interferon gamma

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Expression data from HeLa cells upon interferon-gamma or interferon-beta treatment

Project description:Immune interferon beta and gamma are essential for mammalian host defence against intracellular pathogens. We used microarrays to detail the global programme of gene expression upon interferon-gamma or interferon-beta treatment and identified distinct classes of up-regulated genes.

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Transcription profiling of Toxoplasma-infected human fibroblasts treated with human recombinant interferon gamma

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2007-06-06 | E-SMDB-3827 | biostudies-arrayexpress

Conserved interferon-gamma signaling and decreased immune exclusion programs in responses to immune checkpoint blockade therapy

Project description:We analyzed baseline and on-therapy tumor biopsies from 101 patients with advanced melanoma treated with nivolumab (anti-PD-1) alone or combined with ipilimumab (anti-CTLA-4). Analysis of whole transcriptome data showed that T cell infiltration and interferon-gamma signaling signatures corresponded most highly with clinical response to therapy, with a reciprocal decrease in cell cycle and WNT signaling pathways in responding biopsies. Clinical outcome differences were likely not due to differential melanoma cell responses to interferon-gamma, as 57 human melanoma cell lines exposed in vitro to this cytokine showed a conserved interferon-gamma transcriptome response unless they had mutations that precluded signaling from the interferon-gamma receptor. Therefore, the magnitude of the antitumor T cell response and the corresponding downstream interferon-gamma signaling are the main drivers of clinical response or resistance to immune checkpoint blockade therapy.

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Interferon-gamma signaling promotes melanoma progression and metastasis

Project description:To investigate the effect of Interferon-gamma signaling on gene expression in melanoma cells We performed gene expression analysis of mouse melanoma cell lines that have been treated with Interferon-gamma cytokine as compared with mock-treated controls.

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RNA-seq of mouse intestinal organoids treated with interferon-gamma

Project description:We aimed to investigate gene expression changes in intestinal organoids from different mouse genotypes after treatment with interferon-gamma. Wild-type, villinCreER;KrasG12D/+;Trp53fl/flRosa26N1icd/+ (KPN), and villinCreER;Apcfl/fl;KrasG12D/+;Trp53fl/flTgfbrIfl/fl (AKPT) intestinal organoids were plated, and the media was supplemented with 1 ng/mL of recombinant mouse interferon-gamma protein on Day 3. RNA was collected 24h later and processed for RNA sequencing.

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