title: Negative role of inducible PD-1 on survival of activated dendritic cells.
abstract: PD-1 is a well-established negative regulator of T cell responses by inhibiting proliferation and cytokine production of T cells via interaction with its ligands, B7-H1 (PD-L1) and B7-DC (PD-L2), expressed on non-T cells. Recently, PD-1 was found to be expressed in innate cells, including activated DCs, and plays roles in suppressing production of inflammatory cytokines. In this study, we demonstrate that PD-1 KO DCs exhibited prolonged longevity compared with WT DCs in the dLNs after transfer of DCs into hind footpads. Interestingly, upon LPS stimulation, WT DCs increased the expression of PD-1 and started to undergo apoptosis. DCs, in spleen of LPS-injected PD-1 KO mice, were more resistant to LPS-mediated apoptosis in vivo than WT controls. Moreover, treatment of blocking anti-PD-1 mAb during DC maturation resulted in enhanced DC survival, suggesting that PD-1:PD-L interactions are involved in DC apoptosis. As a result, PD-1-deficient DCs augmented T cell responses in terms of antigen-specific IFN-γ production and proliferation of CD4 and CD8 T cells to a greater degree than WT DCs. Moreover, PD-1 KO DCs exhibited increased MAPK1 and CD40-CD40L signaling, suggesting a possible mechanism for enhanced DC survival in the absence of PD-1 expression. Taken together, our findings further extend the function of PD-1, which plays an important role in apoptosis of activated DCs and provides important implications for PD-1-mediated immune regulation.
authors: 1.Pohang University of Science & Technology (POSTECH), San 31 Hyoja Dong, Namgu, Pohang, Korea. ycsung@postech.ac.kr.
authors: Seong Jeong
authors: SJ
authors: Park
authors: Hong
authors: H
authors: Namkoong
authors: Junsang
authors: J
authors: Doh
authors: Jong-Cheol
authors: JC
authors: Choi
authors: Bo-Gie
authors: BG
authors: Yang
authors: Yunji
authors: Y
authors: Park
authors: Young
authors: Y
authors: Chul Sung
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017209:Apoptosis; D019013:CD40 Antigens / Q000502:physiology; D023201:CD40 Ligand / Q000502:physiology; D002470:Cell Survival; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000502:physiology; D061026:Programmed Cell Death 1 Receptor / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D019013:CD40 Antigens; D008070:Lipopolysaccharides; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D023201:CD40 Ligand; C535148:Mapk1 protein, mouse; D019950:Mitogen-Activated Protein Kinase 1
keywords: LPS; apoptosis; immune regulator; inhibitory