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Record W4385351665 · doi:10.1016/j.immuni.2023.07.002

Ketolysis drives CD8+ T cell effector function through effects on histone acetylation

2023· article· en· W4385351665 on OpenAlexafffund
Katarzyna M. Luda, Joseph Longo, Susan M. Kitchen-Goosen, Lauren R. Duimstra, H. Eric, McLane J. Watson, Brandon M. Oswald, Zhen Fu, Zachary Madaj, Ariana Kupai, Bradley M. Dickson, Lisa M. DeCamp, Michael S. Dahabieh, Shelby E. Compton, Robert Teis, Irem Kaymak, Kin H. Lau, Daniel P. Kelly, Patrycja Puchalska, Kelsey S. Williams, Connie M. Krawczyk, Dominique Lévesque, François‐Michel Boisvert, Ryan D. Sheldon, Scott B. Rothbart, Peter A. Crawford, Russell G. Jones

Bibliographic record

VenueImmunity · 2023
Typearticle
Languageen
FieldMedicine
TopicDiet and metabolism studies
Canadian institutionsUniversité de Sherbrooke
FundersNational Institute of Allergy and Infectious DiseasesNational Institute of General Medical SciencesNational Institute of Diabetes and Digestive and Kidney DiseasesNational Heart, Lung, and Blood InstituteFonds de Recherche du Québec - SantéCanadian Institutes of Health ResearchNational Institute on AgingNational Cancer InstituteNational Institutes of Health
KeywordsAcetylationEffectorBiologyHistoneCell biologyFunction (biology)CD8Cancer researchImmunologyGeneticsImmune systemGene

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.019
GPT teacher head0.294
Teacher spread0.276 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations124
Published2023
Admission routes2
Has abstractyes

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