Evidence map›Paper›PMID 41068616›Full record

ArticleMolecular medicine (Cambridge, Mass.)2025

Dysfunctional glycolysis-UCP2-fatty acid oxidation promotes CTLA4

Jiawen Han, Zhongyang Zhou, Hongxia Wang, Yuxin Chen, Wuguo Li, Meiqin Dai, Jing Bian, Erming Zhao, Jiaying He, Xinyao Zhang and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular medicine (Cambridge, Mass.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Review
  2. Research Progress of Molecular HDrug design, development and therapy · 2026
    Review
  3. Review
  4. Review
  5. 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

12 authors.

Jiawen Han *The Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, P. R. of China.
Zhongyang Zhou *The Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, P. R. of China.
Hongxia Wang *Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, P.R. of China.
Yuxin Chen *Department of Laboratory Medicine, Affiliated Hospital of Medical School, Nanjing Drum Tower Hospital, Nanjing University, Nanjing, 210008, P. R. of China.
Wuguo LiThe Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, P. R. of China.
Meiqin DaiThe Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, P. R. of China.
Jing BianThe Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, P. R. of China.
Erming ZhaoThe Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, P. R. of China.
Jiaying HeThe Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, P. R. of China.
Xinyao ZhangDepartment of Urology, Henan Cancer Hospital, Zhengzhou, 450008, P.R. of China.
Huanfa YiCentral Laboratory, The First Hospital of Jilin University, Changchun, 130061, P.R. of China.
Lan ShaoThe Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, P. R. of China. shaolan@mail.sysu.edu.cn.

Funding

Guangdong Natural Science Foundation 2024A1515013200National Natural Science Foundation of China 82071818
6 · The paper itself

Abstract

In rheumatoid arthritis (RA), the impaired function of regulatory T cells (Tregs) induces chronic inflammatory responses in the synovium. Cytotoxic T Lymphocyte Antigen 4 (CTLA4) is crucial for Sustaining Treg function. Uncoupling Protein 2 (UCP2) plays a key role in linking the glycolysis and fatty acid oxidation (FAO) pathways. Here we observed that Tregs in RA were predominantly characterized by a CD25intCTLA4intFOXP3intCD4high Phenotype. Mechanistically, elevated expression of UCP2 in RA Tregs disrupted metabolic homeostasis by downregulating Carnitine Palmitoyltransferase 2 (CPT2), a rate-limiting enzyme in the FAO pathway. Impaired FAO trigged caveolae-mediated endocytosis, leading to reduced CTLA4 cell surface accumulation and diminished Treg suppressive capacity. Moreover, UCP2 inhibition attenuated the pro-inflammatory effects of RA T cells in a human-SCID chimeric mouse model. Our results establish a critical link between CTLA4 endocytosis and UCP2-mediated metabolic shift in Tregs and identified UCP2 as a potential therapeutic target for preventing RA autoimmunity.

Indexed as

Arthritis, RheumatoidCTLA-4 AntigenFatty AcidsGlycolysisT-Lymphocytes, RegulatoryUncoupling Protein 2AnimalsFemaleForkhead Transcription FactorsHumansMiceOxidation-ReductionCTLA-4 AntigenCTLA4 protein, humanFatty AcidsForkhead Transcription FactorsUCP2 protein, humanUncoupling Protein 2CaveolaeCTLA4Fatty acid β-oxidationGlycolysisRheumatoid arthritisTregUCP2

Identifiers

PMID41068616
PMCPMC12512393

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Registered trials

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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 OpenQuestion graph.