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Ketolysis is a metabolic driver of CD8+ T cell effector function through histone acetylation.

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE229359 | GEO | 2025/07/09

REPOSITORIES: GEO

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Ketolysis is a metabolic driver of CD8+ T cell effector function through histone acetylation

Project description:Environmental nutrient availability influences T cell metabolism, impacting T cell function and shaping immune outcomes. However, the metabolic pathways critical for optimal T cell responses remain poorly understood. Here, we identify ketone bodies (KBs) – including -hydroxybutyrate (OHB) and acetoacetate (AcAc) – as essential fuels supporting CD8+ T cell metabolism and effector function. Ketolysis is an intrinsic feature of highly functional CD8+ T effector (Teff) cells and OHB directly increases CD8+ Teff cell IFN- production and cytolytic activity. Using metabolic tracers, we establish that CD8+ Teff cells preferentially use KBs over glucose to fuel the tricarboxylic acid (TCA) cycle in vitro and in vivo. KBs directly boost the respiratory capacity of CD8+ T cells and TCA cycle-dependent metabolic pathways that fuel T cell growth. Mechanistically, we find that OHB is a major substrate for acetyl-CoA production in CD8+ T cells and regulates effector responses through effects on histone acetylation. Together, our results identify cell-intrinsic ketolysis as a metabolic and epigenetic driver of optimal CD8+ T cell effector responses.

2023-10-11 | PXD036292 | Pride

Ketolysis is a metabolic driver of CD8+ T cell effector function through histone acetylation

Project description:Investigating the effect of reducing ketolytic capacity on the transcriptional profile of CD8 T cells responding to listeria infection in vivo

2025-07-09 | GSE212048 | GEO

Ketolysis is a metabolic driver of CD8+ T cell effector function through histone acetylation [ChIP-seq]

Project description:Investigating the effects of Bdh1 deletion on acetylation of lysine 27 on histone 3 (H3K27ac) in CD8+ T cells 24 h post-activation with anti-CD3 and anti-CD28 antibodies

2025-07-09 | GSE229358 | GEO

Ketolysis drives CD8<sup>+</sup> T cell effector function through effects on histone acetylation.

Project description:Environmental nutrient availability influences T cell metabolism, impacting T cell function and shaping immune outcomes. Here, we identified ketone bodies (KBs)-including β-hydroxybutyrate (βOHB) and acetoacetate (AcAc)-as essential fuels supporting CD8+ T cell metabolism and effector function. βOHB directly increased CD8+ T effector (Teff) cell cytokine production and cytolytic activity, and KB oxidation (ketolysis) was required for Teff cell responses to bacterial infection and tumor challenge. CD8+ Teff cells preferentially used KBs over glucose to fuel the tricarboxylic acid (TCA) cycle in vitro and in vivo. KBs directly boosted the respiratory capacity and TCA cycle-dependent metabolic pathways that fuel CD8+ T cell function. Mechanistically, βOHB was a major substrate for acetyl-CoA production in CD8+ T cells and regulated effector responses through effects on histone acetylation. Together, our results identify cell-intrinsic ketolysis as a metabolic and epigenetic driver of optimal CD8+ T cell effector responses.

| S-EPMC10528215 | biostudies-literature

Ketolysis is a metabolic driver of CD8+ T cell effector function through histone acetylation

Project description:Ketolysis is a metabolic driver of CD8+ T cell effector function through histone acetylation

| PRJNA873701 | ENA

Ketolysis is a metabolic driver of CD8+ T cell effector function through histone acetylation.

Project description:Ketolysis is a metabolic driver of CD8+ T cell effector function through histone acetylation.

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Ketolysis is a metabolic driver of CD8+ T cell effector function through histone acetylation [ChIP-seq]

Project description:Ketolysis is a metabolic driver of CD8+ T cell effector function through histone acetylation [ChIP-seq]

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Regulation of NK effector function by ACLY-generated acetylation

Project description:This SuperSeries is composed of the SubSeries listed below.

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Canagliflozin impairs T-cell effector function via metabolic suppression in autoimmunity.

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-04-04 | GSE228911 | GEO

Krüppel-like factor 4 regulates the cytolytic effector function of exhausted CD8 T-cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-10-24 | GSE212806 | GEO

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