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...

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Bibliographic Details
Published inNature immunology Vol. 5; no. 6; pp. 583 - 589
Main Authors Hou, Wu-Shiun, Van Parijs, Luk
Format Journal Article
LanguageEnglish
Published United States Nature Publishing Group 01.06.2004
Subjects
Animals
Biological Clocks - immunology
Biological Clocks - physiology
Cell Survival - immunology
Cell Survival - physiology
Dendritic Cells - immunology
Dendritic Cells - physiology
Homeostasis - physiology
Immunogenicity
Life span
Mice
Pathogens
Proto-Oncogene Proteins c-bcl-2 - immunology
Proto-Oncogene Proteins c-bcl-2 - physiology
Survival
T-Lymphocytes - immunology
T-Lymphocytes - physiology
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Summary: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.
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ISSN:1529-2908
1529-2916
DOI:10.1038/ni1071