Evidence map›Paper›PMID 40879484›Full record

ArticleHepatology communications2025

Fatty acid β-oxidation enhances immune regulatory function of double-negative T cells through pSTAT4-OX40 signaling pathway.

Zeyu Wang, Yuan Jiang, Longyang Zhou, Xinjie Zhong, Jingjing Zhu, Jie Sun, Xiaotong Han, Hua Jin, Dong Zhang, Guangyong Sun

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Hepatology communications, 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

10 authors.

Zeyu WangMedical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.ORCID 0000-0003-4048-2609
Yuan JiangMedical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Longyang ZhouMedical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Xinjie ZhongMedical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Jingjing ZhuMedical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Jie SunMedical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Xiaotong HanMedical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Hua JinMedical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Dong ZhangMedical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Guangyong SunMedical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDouble-negative T (DNT) cells (CD3+CD4-CD8-NK1.1-) demonstrate immunoregulatory functions in maintaining hepatic immune homeostasis. This study investigates how energy metabolism impacts DNT cell survival and immunoregulatory functions, exploring potential therapeutic applications for autoimmune hepatitis.

methodsWe compared DNT cells with conventional CD4+ T cells through lipidomic analysis, fatty acid β-oxidation (FAO) assessment, and single-cell RNA sequencing. Cells were treated with fatty acids (oleic acid and palmitic acid) and the FAO inhibitor Etomoxir (Eto). We evaluated cell survival, proliferation, and function through flow cytometry and reverse transcription-quantitative polymerase chain reaction. Transcriptome sequencing identified key regulatory molecules. The therapeutic potential was assessed in a Concanavalin A (ConA)-induced autoimmune hepatitis mouse model receiving DNT and DNT-Eto cell treatments.

resultsDNT cells showed higher fatty acid content, FAO levels, and related gene expression compared with CD4+ T cells. Fatty acid supplementation enhanced DNT cell proliferation and immunoregulatory function, whereas FAO inhibition significantly impaired cell survival and function. Transcriptome analysis identified OX40 as a key regulator of DNT cell survival and function, regulated by FAO-activated pSTAT4. In the ConA-induced murine model, therapeutic administration of DNT cells significantly ameliorated the severity of autoimmune hepatitis compared with the ConA-treated control group. Meanwhile, DNT-Eto-treated groups showed more severe liver injury and elevated liver enzymes compared with DNT-treated groups. In vivo analyses revealed that DNT cells exhibited superior survival, function, and CD4+ T cell inhibition compared with Eto-treated or OX40 KO-DNT cells.

conclusionsFAO regulates DNT cell survival and immunoregulatory function through the pSTAT4-OX40 pathway, enhancing their protective effect against autoimmune hepatitis.

Indexed as

Fatty AcidsHepatitis, AutoimmuneReceptors, OX40STAT4 Transcription FactorAnimalsCD4-Positive T-LymphocytesCell ProliferationCell SurvivalConcanavalin ADisease Models, AnimalEpoxy CompoundsMaleMiceMice, Inbred C57BLOX40 LigandOxidation-ReductionConcanavalin AEpoxy CompoundsetomoxirFatty AcidsOX40 LigandReceptors, OX40STAT4 Transcription FactorTnfrsf4 protein, mouseTnfsf4 protein, mouseautoimmune hepatitisdouble-negative T cellenergy metabolismfatty acid β-oxidationimmunoregulatory

Identifiers

PMID40879484
PMCPMC12401205

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.