Targeting the Mapk13‐Tcf1‐Slc7a5 Axis via One‐Carbon Metabolic Regulation to Prevent Chronic Allograft Vasculopathy
Year: 2026
Type: article
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: Advanced Science
Authors: Wang Yi, Di Wu, Jing Liu, Shi Chen, Liu Song, Bin Xie, Aini Xie, Peixiang Lan, Zhishui Chen
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,730
OpenAlex ID: W7124279415