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

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 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.

Regulation of Dendritic Cell Immune Function and Metabolism by Cellular Nutrient Sensor Mammalian Target of Rapamycin (mTOR)

“…Nevertheless, the regulation of lipid metabolism in DCs has clear immunological relevance as there are notable instances where parasite infection of DCs leads to significant changes in lipid metabolism (41). In addition, LPS stimulation leads to specific increases in cellular ceramide concentration in DCs and immunogenic DCs and tolerogenic DCs display unique intracellular lipid profiles (42). With respect to cholesterol lipid metabolism, it is clear that this too is a highly important process in DCs.…”

Critical Shifts in Cerebral White Matter Lipid Profiles After Ischemic–Reperfusion Brain Injury in Fetal Sheep as Demonstrated by the Positive Ion Mode MALDI-Mass Spectrometry

“…In the present study, in light of the prominently increased expression of SM, the selective increase in GlcCer (40:1) may have resulted from de novo synthesis in injured oligodendroglial cells. Alternatively, it could have been driven by the influx of inflammatory cells associated with responses to I/R injury 57 .…”

Estudio lipidómico de la activación y maduración de células dendríticas. Efecto del ácido araquidónico y de los isómeros del ácido hexadecenoico

“…embargo, sí observaron cambios en especies individuales de lípidos, tales como aumentos en ceramidas (Cer) y en fosfatidilcolina (PC) y disminuciones en esfingomielina (SM), fofatidiletanolamina (PE) y fosfatidilglicerol (PG). Otros estudios realizados en células dendríticas de ratón(285,286) han observado también cambios en especies de lípidos, pero no en su contenido total, como aumentos en PC y Cer y disminuciones en SM y PI.…”