Tolerogenic versus Immunogenic Lipidomic Profiles of CD11c+ Immune Cells and Control of Immunogenic Dendritic Cell Ceramide Dynamics

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Carlos Ocaña-Morgner - , Institute of Physiological Chemistry (Author)
  • Susanne Sales - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Manuela Rothe - , Medical Faculty Carl Gustav Carus (Author)
  • Andrej Shevchenko - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Rolf Jessberger - , Institute of Physiological Chemistry (Author)

Abstract

Lipids affect the membrane properties determining essential biological processes. Earlier studies have suggested a role of switch-activated protein 70 (SWAP-70) in lipid raft formation of dendritic cells. We used lipidomics combined with genetic and biochemical assays to analyze the role of SWAP-70 in lipid dynamics. TLR activation using LPS as a ligand represented a pathogenic immunogenic stimulus, physical disruption of cell-cell contacts a tolerogenic stimulus. Physical disruption, but not LPS, caused an increase of phosphatidylcholine ether and cholesteryl esters in CD11c+ immune cells. An increase of ceramide (Cer) was a hallmark for LPS activation. SWAP-70 was required for regulating the increase and localization of Cers in the cell membrane. SWAP-70 controls Cer accumulation through the regulation of pH-dependent acid-sphingomyelinase activity and of RhoA-dependent transport of endosomal contents to the plasma membrane. Poor accumulation of Cers in Swap70-/- cells caused decreased apoptosis. This shows that two different pathways of activation, immunogenic and tolerogenic, induce different changes in the lipid composition of cultured CD11c+ cells, and highlights the important role of SWAP-70 in Cer dynamics in dendritic cells.

Details

Original languageEnglish
Pages (from-to)4360-4372
Number of pages13
JournalJournal of Immunology
Volume198
Issue number11
Publication statusPublished - 1 Jun 2017
Peer-reviewedYes

External IDs

Scopus 85019844508
PubMed 28468968

Keywords

Keywords

  • Animals, Apoptosis, CD11c Antigen/immunology, Cell Line, Cells, Cultured, Ceramides/immunology, Cholesterol Esters/genetics, Culture Media/chemistry, Cytokines/biosynthesis, DNA-Binding Proteins/genetics, Dendritic Cells/drug effects, Guanine Nucleotide Exchange Factors/genetics, Immune Tolerance, Lipids/analysis, Lipopolysaccharides/immunology, Mice, Minor Histocompatibility Antigens/genetics, Nuclear Proteins/genetics, Sphingomyelin Phosphodiesterase/metabolism