| First Author | Stathopoulou C | Year | 2018 |
| Journal | Immunity | Volume | 49 |
| Issue | 2 | Pages | 247-263.e7 |
| PubMed ID | 30054205 | Mgi Jnum | J:353114 |
| Mgi Id | MGI:6706556 | Doi | 10.1016/j.immuni.2018.05.006 |
| Citation | Stathopoulou C, et al. (2018) PD-1 Inhibitory Receptor Downregulates Asparaginyl Endopeptidase and Maintains Foxp3 Transcription Factor Stability in Induced Regulatory T Cells. Immunity 49(2):247-263.e7 |
| abstractText | 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(+)iTregPDL1 cells) and inducible regulatory T (iTreg) cells. Tbet(+)iTregPDL1 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(+)iTregPDL1 cells and iTreg cells by specifically downregulating endo-lysosomal protease asparaginyl endopeptidase (AEP). AEP regulated Foxp3 stability and blocking AEP imparted regulatory function in Tbet(+)iTreg cells. Also, Aep(-/-) iTreg cells significantly inhibited GvHD and maintained Foxp3 expression. PD-1-mediated Foxp3 maintenance in Tbet(+) Th1 cells occurred both in tumor infiltrating lymphocytes (TILs) and during chronic viral infection. Collectively, this report has identified an intrinsic function for PD-1 in maintaining Foxp3 through proteolytic pathway. |
