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PMID: 18166652 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Regulation of translation is required for dendritic cell function and survival during activation.

The Journal of cell biology ·Vol. 179 ·No. 7 ·2007-12-31 ·Pages 1427-39

Lelouard H, Schmidt EK, Camosseto V, Clavarino G, Ceppi M, Hsu HT, Pierre P

Abstract

In response to inflammatory stimulation, dendritic cells (DCs) have a remarkable pattern of differentiation (maturation) that exhibits specific mechanisms to control antigen processing and presentation. Here, we show that in response to lipopolysaccharides, protein synthesis is rapidly enhanced in DCs. This enhancement occurs via a PI3K-dependent signaling pathway and is key for DC activation. In addition, we show that later on, in a manner similar to viral or apoptotic stress, DC activation leads to the phosphorylation and proteolysis of important translation initiation factors, thus inhibiting cap-dependent translation. This inhibition correlates with major changes in the origin of the peptides presented by MHC class I and the ability of mature DCs to prevent cell death. Our observations have important implications in linking translation regulation with DC function and survival during the immune response.

MeSH Terms
Animals Antigen Presentation/genetics Cell Differentiation/genetics Cell Survival/genetics Cells, Cultured Codon, Terminator/genetics Dendritic Cells/physiology Eukaryotic Initiation Factors/genetics,metabolism Histocompatibility Antigens Class I/metabolism Immunity, Cellular/genetics Inflammation/genetics,metabolism Lipopolysaccharides/pharmacology Lymphocyte Activation/genetics Male Mice Mice, Inbred C57BL Phosphatidylinositol 3-Kinases/metabolism Protein Biosynthesis/genetics Signal Transduction/physiology Up-Regulation/genetics
Chemicals
Codon, Terminator Eukaryotic Initiation Factors Histocompatibility Antigens Class I Lipopolysaccharides Phosphatidylinositol 3-Kinases
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Lelouard Hugues
Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, Case 906, 13288 Marseille, France.
Schmidt Enrico K
Camosseto Voahirana
Clavarino Giovanna
Ceppi Maurizio
Hsu Hsiang-Ting
Pierre Philippe
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
1540-8140
DOI
10.1083/jcb.200707166
Published
2007-12-31
Pages
1427-39
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2373495
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.200707166 PMC Full Text View journal details
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