Acetyl-CoA carboxylase 1 inhibition increases Treg metabolism and graft-versus-host disease treatment efficacy via mitochondrial fusion.

ABSTRACT: Tregs are critical for maintaining immune homeostasis, and their adoptive transfer can treat murine inflammatory disorders. In patients, Treg therapies have been variably efficacious. Therefore, new strategies to enhance Treg therapeutic efficacy are needed. Tregs predominantly depend on oxidative phosphorylation (OXPHOS) for energy and suppressive function. Fatty acid oxidation (FAO) contributes to Treg OXPHOS and can be important for Treg "effector" differentiation, but FAO activity is inhibited by coordinated activity of the isoenzymes acetyl-CoA carboxylase-1 and -2 (ACC1 and ACC2). Here, we show that small-molecule inhibition or Treg-specific genetic deletion of ACC1 significantly increases Treg suppressive function in vitro and in mice with established chronic graft-versus-host disea

SUBMITTER: McDonald-Hyman C 

PROVIDER: S-EPMC12646659 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature