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Lookup NU author(s): Chaido Stathopoulou, Grace Mallett, Luke Liniany, Dr Rolando Berlinguer PalminiORCiD, Dr Arian Laurence, Dr Shoba AmarnathORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
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+iTregPDL1cells) and inducible regulatory T cells (iTregs). Tbet+iTregPDL1cells 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+iTregPDL1cells 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
Author(s): 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
Publication type: Article
Publication status: Published
Journal: Immunity
Year: 2018
Volume: 49
Issue: 2
Pages: 247-263.e7
Print publication date: 21/08/2018
Online publication date: 24/07/2018
Acceptance date: 17/05/2018
Date deposited: 27/06/2018
ISSN (print): 1074-7613
ISSN (electronic): 1097-4180
Publisher: Cell Press
URL: https://doi.org/10.1016/j.immuni.2018.05.006
DOI: 10.1016/j.immuni.2018.05.006
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