PD-1 inhibitory receptor downregulates asparaginyl endopeptidase and maintains Foxp3 transcription factor stability in induced regulatory T cells
| Title: | PD-1 inhibitory receptor downregulates asparaginyl endopeptidase and maintains Foxp3 transcription factor stability in induced regulatory T cells |
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| Authors: | Stathopoulou C; Gangaplara A; Mallett G; Flomerfelt FA; Liniany LP; Knight D; Samsel LA; Berlinguer-Palmini R; Yim J; Felizardo TC; Eckhaus MA; Edgington-Mitchell L; Martinez-Fabregas J; Zhu J; Fowler DH; van Kasteren SI; Laurence A; Bogyo M; Watts C; Shevach EM; Amarnath S |
| Source: | Immunity |
| Publisher Information: | Cell Press |
| Collection: | Newcastle University Library ePrints Service |
| Description: | CD4 + T cell differentiation into multiple T helper cell (Th) 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 cells (iTregs). 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 down regulating 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 (TIL) and during chronic viral infection. Collectively, this report has identified an intrinsic function for PD-1 in maintaining Foxp3 through proteolytic pathway |
| Document Type: | article in journal/newspaper |
| File Description: | application/pdf |
| Language: | unknown |
| Relation: | https://eprints.ncl.ac.uk/249368; https://eprints.ncl.ac.uk/fulltext.aspx?url=249368/D657249B-CAD9-4BFC-A2DF-A3F9E9D67734.pdf&pub_id=249368 |
| Availability: | https://eprints.ncl.ac.uk/249368 |
| Rights: | https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Accession Number: | edsbas.8B3596C2 |
| Database: | BASE |