Evidence mapPaperPMID 39150482Full record

ArticleThe Journal of experimental medicine2024

ACLY and ACSS2 link nutrient-dependent chromatin accessibility to CD8 T cell effector responses.

Irem Kaymak, McLane J Watson, Brandon M Oswald, Shixin Ma, Benjamin K Johnson, Lisa M DeCamp, Batsirai M Mabvakure, Katarzyna M Luda, Eric H Ma, Kin Lau and 18 more

Abstract read
In one paragraph

Article in The Journal of experimental medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed.

  1. New insights into the ACLY-mediated metabolic and epigenetic interplay in macrophages.Journal of enzyme inhibition and medicinal chemistry · 2026
    Review
  2. Review
  3. Review
  4. Article
  5. Metabolic Reprogramming and ILC2 Plasticity in Obesity-related Asthma.Clinical reviews in allergy & immunology · 2026
    Review
  6. Review
  7. Article
  8. Lipid metabolism in homeostasis and disease.Signal transduction and targeted therapy · 2026
    Review
  9. Cancer Stem Cells Shift Metabolite Acetyl-Coenzyme A to Abrogate the Differentiation of CD103Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  10. Review
  11. Review
  12. Review
  13. Review
  14. Review
  15. Review
  16. Review
  17. Dietary restriction reprograms CD8Nature metabolism · 2025
    Article
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

28 authors.

Irem Kaymak *Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA.ORCID 0000-0003-0772-512X
McLane J Watson *Department of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA.ORCID 0000-0001-5778-7690
Brandon M OswaldDepartment of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA.ORCID 0000-0002-4147-2915
Shixin MaNOMIS Center for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies , La Jolla, CA, USA.ORCID 0009-0001-6372-1097
Benjamin K JohnsonDepartment of Epigenetics, Van Andel Institute, Grand Rapids, MI, USA.ORCID 0000-0002-1482-1032
Lisa M DeCampDepartment of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA.ORCID 0000-0002-4682-7586
Batsirai M MabvakureDepartment of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA.ORCID 0000-0002-2760-5443
Katarzyna M LudaDepartment of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA.ORCID 0000-0002-6647-3981
Eric H MaDepartment of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA.ORCID 0000-0001-8556-980X
Kin LauBioinformatics and Biostatistics Core, Van Andel Institute , Grand Rapids, MI, USA.ORCID 0000-0002-7405-1551
Zhen FuBioinformatics and Biostatistics Core, Van Andel Institute , Grand Rapids, MI, USA.ORCID 0000-0002-8120-590X
Brejnev MuhireDepartment of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA.ORCID 0000-0002-5594-1348
Susan M Kitchen-GoosenDepartment of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA.ORCID 0000-0001-9291-056X
Alexandra Vander ArkDepartment of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA.ORCID 0000-0002-1194-810X
Michael S DahabiehDepartment of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA.ORCID 0000-0002-2518-7129
Bozena SamborskaGoodman Cancer Institute, Faculty of Medicine, McGill University , Montréal, Canada.ORCID 0000-0002-1871-4699
Matthew VosDepartment of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA.ORCID 0009-0008-9669-4380
Hui ShenDepartment of Epigenetics, Van Andel Institute, Grand Rapids, MI, USA.ORCID 0000-0001-9767-4084
Zi Peng FanAgios Pharmaceuticals , Cambridge, MA, USA.ORCID 0009-0004-0094-6514
Thomas P RoddyAgios Pharmaceuticals , Cambridge, MA, USA.ORCID 0009-0005-1143-6840
Gillian A KingsburyAgios Pharmaceuticals , Cambridge, MA, USA.ORCID 0009-0002-9117-0824
Cristovão M SousaAgios Pharmaceuticals , Cambridge, MA, USA.ORCID 0009-0005-2195-3307
Connie M KrawczykDepartment of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA.ORCID 0000-0002-2468-5986
Kelsey S WilliamsDepartment of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA.ORCID 0000-0002-4163-5075
Ryan D SheldonMass Spectrometry Core Facility, Van Andel Institute , Grand Rapids, MI, USA.ORCID 0000-0002-1573-9719
Susan M KaechNOMIS Center for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies , La Jolla, CA, USA.ORCID 0000-0003-1674-1420
Dominic G RoyCentre de Recherche du Centre Hospitalier de l'Université de Montréal , Montréal, Canada.ORCID 0000-0002-6044-0118
Russell G JonesDepartment of Metabolism and Nutritional Programming, Van Andel Institute, Grand Rapids, MI, USA.ORCID 0000-0003-2250-4675

Funding

Regulation of memory CD8 T cell developmentR01AI066232 · NIAID · YALE UNIVERSITY · 2005 to 2025
$1.7M
Ketone Body Metabolism in CD8+ T Cell ResponsesR01AI165722 · VAN ANDEL RESEARCH INSTITUTE · 2025 to 2025
$1.3M
Cancer Epigenetics Training (CET) ProgramT32CA251066 · VAN ANDEL RESEARCH INSTITUTE · 2025 to 2025
$495k
Cancer Research InstituteCancer Research Society PJT 192049Chan Zuckerberg InitiativeDaymon Runyon Foundation 2495-23Fonds de Recherche du Québec-SantéNational Institute of Allergy and Infectious Diseases R21AI153997NCI NIH HHS T32 CA251066NCI NIH HHS T32CA251066-01A1NIAID NIH HHS R01 AI066232NIAID NIH HHS R01 AI165722NIAID NIH HHS R21 AI151986NIAID NIH HHS R21 AI153997NIH HHS R01 AI066232Paul G. Allen Frontiers GroupSalk Pioneer Fund
6 · The paper itself

Abstract

Coordination of cellular metabolism is essential for optimal T cell responses. Here, we identify cytosolic acetyl-CoA production as an essential metabolic node for CD8 T cell function in vivo. We show that CD8 T cell responses to infection depend on acetyl-CoA derived from citrate via the enzyme ATP citrate lyase (ACLY). However, ablation of ACLY triggers an alternative, acetate-dependent pathway for acetyl-CoA production mediated by acyl-CoA synthetase short-chain family member 2 (ACSS2). Mechanistically, acetate fuels both the TCA cycle and cytosolic acetyl-CoA production, impacting T cell effector responses, acetate-dependent histone acetylation, and chromatin accessibility at effector gene loci. When ACLY is functional, ACSS2 is not required, suggesting acetate is not an obligate metabolic substrate for CD8 T cell function. However, loss of ACLY renders CD8 T cells dependent on acetate (via ACSS2) to maintain acetyl-CoA production and effector function. Together, ACLY and ACSS2 coordinate cytosolic acetyl-CoA production in CD8 T cells to maintain chromatin accessibility and T cell effector function.

Indexed as

AcetatesAcetyl Coenzyme AATP Citrate (pro-S)-LyaseCD8-Positive T-LymphocytesChromatinMice, Inbred C57BLAcetate-CoA LigaseAcetylationAnimalsCytosolHistonesMiceMice, KnockoutAcetate-CoA LigaseAcetatesAcetyl Coenzyme AACSS2 protein, mouseATP Citrate (pro-S)-LyaseChromatinHistones

Identifiers

PMID39150482
PMCPMC11329787

What Socratic holds

Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.