DataVXAdvanced SciencePaper
journal article·2026-03Open access

Targeting the Mapk13‐Tcf1‐Slc7a5 Axis via One‐Carbon Metabolic Regulation to Prevent Chronic Allograft Vasculopathy

Wang Yi, Di Wu, Jing Liu, Shi Chen, Liu Song, Bin Xie, Aini Xie, Peixiang Lan, Zhishui Chen

Advanced Science· Volume 13· Issue 17
Publisher pageOpen full text
Source abstract

Abstract

ABSTRACT Chronic allograft vasculopathy (CAV) is driven in part by stem‐like CD4 + T cells, but how these cells sustain their progenitor programs during chronic rejection remains unclear. Here, a metabolic‐epigenetic axis is identified in which Mapk13 phosphorylates Tcf1 at T289, enabling Tcf1 to activate the amino acid transporter Slc7a5 and enhance methionine uptake. This rewires one‐carbon metabolism and increases H3K4me3 enrichment at the Tcf7 locus, thereby maintaining stem‐like CD4 + T cells within rejecting grafts. Disruption of this circuit‐via genetic deletion of Mapk13 or Slc7a5, or through dietary methionine restriction‐reduces Tcf1 + CD4 + T cell stemness and prevents CAV in mouse models. These findings reveal the Mapk13‐Tcf1‐Slc7a5 axis as a critical metabolic dependency of pathogenic T cells and highlight one‐carbon metabolism as a promising target to promote long‐term graft survival.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Pluripotent Stem Cells Research · Angiogenesis and VEGF in Cancer · Mesenchymal stem cell research

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Institute of Organ Transplantation Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei China

Key Laboratory of Organ Transplantation Ministry of Education Chinese Academy of Medical Sciences Wuhan Hubei China

NHC Key Laboratory of Organ Transplantation Wuhan Hubei China

Pancreas Center First Affiliated Hospital of Nanjing Medical University Nanjing China

State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases Huazhong University of Science and Technology Wuhan Hubei China

Funding

National Natural Science Foundation of China · Science Fund for Distinguished Young Scholars of Hubei Province

References (24)

Show source-provided references
1. 10.1016/j.ajt.2023.10.01610.1016/j.ajt.2023.10.016 ↗
2. 10.1146/annurev‐immunol‐103019‐08580310.1146/annurev‐immunol‐103019‐085803 ↗
3. 10.1016/j.coi.2020.09.00110.1016/j.coi.2020.09.001 ↗
4. 10.1097/00007890‐200204150‐0001910.1097/00007890‐200204150‐00019 ↗
5. 10.1034/j.1600‐6143.2003.30105.x10.1034/j.1600‐6143.2003.30105.x ↗
6. 10.1111/j.1600‐6143.2006.01309.x10.1111/j.1600‐6143.2006.01309.x ↗
7. 10.1172/jci1046710.1172/jci10467 ↗
8. 10.1146/annurev.immunol.021908.13270610.1146/annurev.immunol.021908.132706 ↗
9. 10.1038/nri330710.1038/nri3307 ↗
10. 10.1136/jitc‐2023‐00836710.1136/jitc‐2023‐008367 ↗
11. 10.1016/j.cmet.2022.02.00310.1016/j.cmet.2022.02.003 ↗
12. 10.1016/j.molcel.2020.09.00610.1016/j.molcel.2020.09.006 ↗
13. 10.7554/eLife.5372510.7554/eLife.53725 ↗
14. 10.1038/s43018‐022‐00348‐310.1038/s43018‐022‐00348‐3 ↗
15. 10.1016/j.cmet.2020.01.00610.1016/j.cmet.2020.01.006 ↗
16. 10.1038/s42255‐022‐00730‐610.1038/s42255‐022‐00730‐6 ↗
17. 10.1038/cmi.2015.3210.1038/cmi.2015.32 ↗
18. 10.1038/s41590‐023‐01682‐z10.1038/s41590‐023‐01682‐z ↗
19. 10.1038/cddis.2017.20710.1038/cddis.2017.207 ↗
20. 10.4049/jimmunol.130092310.4049/jimmunol.1300923 ↗
21. 10.1038/ni.255610.1038/ni.2556 ↗
22. 10.1038/s41586‐020‐2682‐110.1038/s41586‐020‐2682‐1 ↗
23. 10.1038/s42255‐020‐00280‐910.1038/s42255‐020‐00280‐9 ↗
24. 10.1038/s41586‐023‐05780‐810.1038/s41586‐023‐05780‐8 ↗