GSE183667
Acsbg1 dependent mitochondrial fitness is a metabolic checkpoint for tissue Treg cell homeostasis
Regulatory T (Treg) cells, which belong to the CD4 T cell subset, are critical for immunological tolerance and immune homeostasis. Using a combination of RNA-seq and proteome analyses, we found that Acsbg1, a member of ACSL, is selectively expressed in Treg cells. Furthermore, we found that gene loci of Acsbg1 was epigenetically regulated and opened up by Smad2/3 in Treg cells. Deletion of Smad2/3 decreased expression levels of Acsbg1 compared to control T reg cells.  We show that the genetic deletion and pharmacological inhibition of Acsbg1 causes not only mitochondrial dysfunction, but also dampens other metabolic pathways including glycolysis and the TCA-cycle. The extrinsic supplementation of sgAcsbg1 Treg cells with oleoyl-CoA restored the phenotype of the Treg metabolic signature. Furthermore, we also found evidence of this pathway in ST2+ effector Treg cells in the lung, which underlies the enhanced immunosuppressive capacity in the airway inflammation. This study provide a framework of Acsbg1 serving as a metabolic checkpoint governing Treg cell homeostasis and the resolution of lung inflammation. Overall design: Related to Fig 2, RNA-seq was performed to investigate lipid synthesis genes that are specifically upregulated in Treg cells. Related to Fig 3, RNA-seq and ATAC-seq was performed to investigate the role of Smad2/3 on the regulation of Acsl6 gene expression. Related to Fig 5, RNA-seq was performed to investigate the role of Acsbg1 on the gene expression profile of T reg cells.