PD-1 through asparaginyl endopeptidase regulates FoxP3 Stability in Induced Regulatory T cells
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ABSTRACT: CD4+ T cell differentiation into multiple T helper lineages is critical for optimal adaptive immune responses. This report identified a novel intrinsic mechanism by which PD-1 signaling imparted regulatory phenotype to FoxP3+ Th1 cells (denoted as Tbet+iTregPDL1 cells) and iTregs. Tbet+iTregPDL1 cells were capable of preventing inflammation in murine models of experimental colitis and experimental graft versus host disease. PDL-1 binding to PD-1 imparted regulatory function to Tbet+iTregPDL1 cells and iTregs by specifically downregulating an endolysosomal protease asparaginyl endopeptidase (AEP) AEP regulated FoxP3 stability and blocking AEP imparted regulatory function in Tbet+iTregs cells. Also AEP-/- iTregs significantly inhibited GvHD and maintained FoxP3. Furthermore, 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 a novel intrinsic function for PD-1 in converting Th1 cells into Tregs through an intrinsic proteolytic pathway
ORGANISM(S): Mus musculus
PROVIDER: GSE113815 | GEO | 2018/08/30
REPOSITORIES: GEO
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