A Bcl-2-dependent molecular timer regulates the lifespan and immunogenicity of dendritic cells.
The lifespan of antigen-bearing dendritic cells (DCs) is determined by signals from pathogens and T cells. These signals regulate DC survival by modulating expression of Bcl-2 family proteins. Toll-like receptors and T cell costimulatory molecules both trigger a DC survival pathway that is dependent on Bcl-x(L). However, Toll-like receptors uniquely increase expression of Bim and trigger cell death by a pathway that is blocked by Bcl-2. This pathway serves as a molecular 'timer' that sets the lifespan of DCs and regulates the magnitude of T cell responses in vivo. Thus, signals derived from the innate and acquired immune systems control DC lifespan and immunogenicity by distinct molecular mechanisms.
Hou
Wu-Shiun
WS
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Van Parijs
Luk
L
D000818:Animals; D001683:Biological Clocks / Q000276:immunology / Q000502:physiology; D002470:Cell Survival / Q000276:immunology / Q000502:physiology*; D003713:Dendritic Cells / Q000276:immunology* / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology; D051379:Mice; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000276:immunology* / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology
D019253:Proto-Oncogene Proteins c-bcl-2