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

Ocaña-Morgner, Carlos; Sales, Susanne; Rothe, Manuela; Shevchenko, Andrej; Jessberger, Rolf

doi:10.4049/jimmunol.1601928

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

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Ocaña-Morgner, C., Sales, S., Rothe, M., Shevchenko, A., & Jessberger, R. (2017). Tolerogenic versus Immunogenic Lipidomic Profiles of CD11c(+) Immune Cells and Control of Immunogenic Dendritic Cell Ceramide Dynamics. Journal of immunology (Baltimore, Md.: 1950), 198(11), 4360-4372. doi:10.4049/jimmunol.1601928.

Cite as: https://hdl.handle.net/21.11116/0000-0002-8B9A-4

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.