SLC7A5-mediated L-Leu intake control aGVHD and GVT: metabolomics dataset
Description
Metabolomics data and its univariate analysis for study: Restriction of SLC7A5-mediated L-Leu uptake in allogenic T cells efficiently prevents acute graft-versus-host disease and maintains graft-versus tumor response. The amino acid transporter SLC7A5, which mediates the uptake of L-Leu and other essential amino acids in activated T cells and in malignant cells, has become an important target in controlling inflammation and cancer. However, its role in acute graft-versus-host disease (aGVHD) and graft versus tumor (GVT) has not been explored before. In this study, we demonstrate that SLC7A5 genetic deletion affected the activation and proliferation of allogenic T cells, promoted apoptosis and reduced IFNγ and granzyme B secretion by CD4 and CD8 T cells. Genetic deletion of SLC7A5 completely prevented aGVHD-induced lethality in mice but did not control tumor growth. On the other hand, the administration of a L-Leu-free diet efficiently reduced aGVHD mortality in mice by controlling allogenic T cell expansion, inducing apoptosis, and affecting granzyme B secretion. However, CD8 T cells did not fail to activate and secrete IFNγ in the absence of Leu, and showed increase proportion of central memory T cells, which contributed to the GVT response. Genetic deletion of SLC7A5 in T cells severely compromises mTORC1, glycolysis and mitochondrial oxidation. However, L-Leu removal mildly reduced mTORC1 signaling, completely blocked glycolysis but enhanced mitochondrial function, favoring the generation of central memory responses and expression of stemness marker TCF1. Dietary L-Leu restriction prevented the increase of potential proinflammatory metabolites derived from tricarboxylic acid cycle and L-Leu-derived ketogenesis induced by aGVHD. Overall, this study reveals that dietary restriction of L-Leu is sufficient to target SLC7A5 in allogenic cells during aGVHD, preserving GVT response.