Evidence map›Paper›PMID 40853248›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2025

ACLY promotes NK cell effector function by regulating glycolysis and histone acetylation.

Hyogon Sohn, Ana Kolicheski, Jennifer Poursine-Laurent, Jennifer Tran, Yongjun Wang, Kelly Gan, Joshua M Tobin, Nermina Saucier, Todd A Fehniger, Jacqueline E Payton and 1 more

Abstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Review
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

11 authors.

Hyogon SohnDepartment of Pediatrics, Division of Rheumatology and Immunology, Washington University in St Louis, St Louis, MO, United States.
Ana KolicheskiDepartment of Pediatrics, Division of Rheumatology and Immunology, Washington University in St Louis, St Louis, MO, United States.
Jennifer Poursine-LaurentDepartment of Pediatrics, Division of Rheumatology and Immunology, Washington University in St Louis, St Louis, MO, United States.
Jennifer TranDepartment of Medicine, Division of Oncology, Washington University in St Louis, St Louis, MO, United States.ORCID 0000-0001-5339-1218
Yongjun WangDepartment of Pediatrics, Division of Rheumatology and Immunology, Washington University in St Louis, St Louis, MO, United States.
Kelly GanDepartment of Pediatrics, Division of Rheumatology and Immunology, Washington University in St Louis, St Louis, MO, United States.
Joshua M TobinDepartment of Pediatrics, Division of Rheumatology and Immunology, Washington University in St Louis, St Louis, MO, United States.
Nermina SaucierDepartment of Pediatrics, Division of Rheumatology and Immunology, Washington University in St Louis, St Louis, MO, United States.
Todd A FehnigerDepartment of Medicine, Division of Oncology, Washington University in St Louis, St Louis, MO, United States.
Jacqueline E PaytonDepartment of Pathology and Immunology, Washington University in St Louis, St Louis, MO, United States.ORCID 0000-0001-8832-3661
Megan A CooperDepartment of Pediatrics, Division of Rheumatology and Immunology, Washington University in St Louis, St Louis, MO, United States.ORCID 0000-0002-5696-172X

Funding

Washington University Center for Cellular ImagingP30CA091842 · NCI · WASHINGTON UNIVERSITY · PI TIMOTHY J. EBERLEIN · 2001 to 2026
$128.0M
Targeting the Bone Marrow Microenvironment In Acute Lymphocytic LeukemiaP50CA171963 · NCI · WASHINGTON UNIVERSITY · PI Daniel C Link · 2013 to 2026
$31.6M
METABOLIC REGULATION OF NATURAL KILLER CELL ACTIVATIONR01AI127752 · NIAID · WASHINGTON UNIVERSITY · PI COOPER, MEGAN ANNE · 2017 to 2021
$1.9M
CDI Center for Pediatric ImmunologyCDI Center for Pediatric Immunology at Washington University in St LouisLeukemia and Lymphoma SocietyNational Cancer Institute Cancer Center #P30 CA091842NCI NIH HHS #P30 CA091842NCI NIH HHS P30 CA091842NCI NIH HHS P50 CA171963NIAID NIH HHS R01 AI127752NIH HHS P50CA171963NIH HHS R01AI127752Siteman Flow CytometryWashington University School of Medicine in St Louis
6 · The paper itself

Abstract

Natural killer (NK) cells are innate immune lymphocytes important for host viral and tumor immunity. We investigated the requirement for ATP citrate lyase (ACLY) in NK cell function using an inducible genetic mouse model. ACLY regulates the citrate-malate shuttle, generating cytosolic acetyl-coenzyme A that is primarily used for acetylation or lipid synthesis. ACLY-deficient NK cells upon IL-15 activation exhibited significant defects in glycolysis, proliferation, cytokine production, and cytotoxicity, without decreased intracellular lipids. Notably, ACLY deficiency specifically resulted in reduced NK cell responses to activating receptors associated with the adapter proteins DAP10 or DAP12. This is due to decreased DAP12 and increased DAP10 transcript and protein, coupled with epigenetic profiling that demonstrated altered histone acetylation of these genes in ACLY KO. Supplementation of ACLY-deficient NK cells with acetate was sufficient to overcome most functional defects, including restoring DAP10/12 expression and activating receptor function, emphasizing the importance of ACLY-generated cytosolic acetyl-coenzyme A for NK effector functions.

Indexed as

ATP Citrate (pro-S)-LyaseGlycolysisHistonesKiller Cells, NaturalAcetylationAcetyl Coenzyme AAnimalsInterleukin-15Lymphocyte ActivationMiceMice, Inbred C57BLMice, KnockoutAcetyl Coenzyme AATP Citrate (pro-S)-LyaseHistonesInterleukin-15cell activationcytokinesepigeneticsnatural killer cellsrodent

Identifiers

PMID40853248
PMCPMC12380160

What Socratic holds

Textmetadata
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.