PD-1 Inhibitory Receptor Downregulates Asparaginyl Endopeptidase and Maintains Foxp3 Transcription Factor Stability in Induced Regulatory T Cells.

ABSTRACT: CD4⁺ T cell differentiation into multiple T helper (Th) cell lineages is critical for optimal adaptive immune responses. This report identifies an intrinsic mechanism by which programmed death-1 receptor (PD-1) signaling imparted regulatory phenotype to Foxp3⁺ Th1 cells (denoted as Tbet⁺iTreg_PDL1 cells) and inducible regulatory T (iTreg) cells. Tbet⁺iTreg_PDL1 cells prevented inflammation in murine models of experimental colitis and experimental graft versus host disease (GvHD). Programmed death ligand-1 (PDL-1) binding to PD-1 imparted regulatory function to Tbet⁺iTreg_PDL1 cells and iTreg cells by specifically downregulating endo-lysosomal protease asparaginyl endopeptidase (AEP). AEP regulated Foxp3 st

SUBMITTER: Stathopoulou C 

PROVIDER: S-EPMC6105434 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature