Profiling changes triggered during maturation of dendritic cells: a lipidomic approach

Abstract

Lipids are important in several biological processes because they act as signalling and regulating molecules, or, locally, as membrane components that modulate protein function. This paper reports the pattern of lipid composition of dendritic cells (DCs), a cell type of critical importance in inflammatory and immune responses. After activation by antigens, DCs undergo drastic phenotypical and functional transformations, in a process known as maturation. To better characterize this process, changes of lipid profile were evaluated by use of a lipidomic approach. As an experimental model of DCs, we used a foetal skin-derived dendritic cell line (FSDC) induced to mature by treatment with lipopolysaccharide (LPS). The results showed that LPS treatment increased ceramide (Cer) and phosphatidylcholine (PC) levels and reduced sphingomyelin (SM) and phosphatidylinositol (PI) content. Mass spectrometric analysis of a total lipid extract and of each class of lipids revealed that maturation promoted clear changes in ceramide profile. Quantitative analysis enabled identification of an increase in the total ceramide content and enhanced Cer at m/z 646.6, identified as Cer(d18:1/24:1), and at m/z 648.6, identified as Cer(d18:1/24:0). The pattern of change of these lipids give an extremely rich source of data for evaluating modulation of specific lipid species triggered during DC maturation.

A Ceramide Analogue Stimulates Dendritic Cells To Promote T Cell Responses upon Virus Infections

“…Lipidomic profiling has shown that DCs upregulate the production of C24 ceramide upon LPS stimulation (17). Further, inflammatory cytokines such as TNF-α elevate the level of ceramide in DCs (59).…”

“…Further, inflammatory cytokines such as TNF-α elevate the level of ceramide in DCs (59). However, a role for this increase in ceramide content has not yet been elucidated (17). Exogenous C2 ceramide was reported to inhibit the ability of human DCs to take up soluble antigens to impair their ability to stimulate the antigen-specific T cell clones in vitro (60).…”

“…Moreover, it was shown that the cross-linking of CD28 activates acid sphingomyelinase, which enhances the transmission of the signal to NF-κB in Jurkat T cells (16). In a recent lipidomic study, an increase in the production of 24-carbon ceramide has been demonstrated to occur during LPS-induced dendritic cell maturation which again suggests roles for ceramide or ceramide metabolizing enzymes during immune responses (17). However it has also been shown that ceramide can inhibit the production of inflammatory cytokines from LPS-stimulated mast cells (18).…”

Sphingolipids and Inflammatory Diseases of the Skin

“…It has been indicated that stimulation of DCs with proinflammatory molecules like LPS, TNF-α or IL-1β increased intracellular levels of ceramide (Santinha et al 2012). This increase leads to the suggestion that a ceramide-mediated pathway is responsible for some of the functional alterations observed during the maturation process.…”

Intratracheal myriocin enhances allergen‐induced Th2 inflammation and airway hyper‐responsiveness

“…1A). Macrophages and dendritic cells are known to dynamically regulate intracellular sphingolipid metabolism during activation, increasing their intracellular ceramide concentrations via both sphingomyelin hydrolysis or de novo synthesis [18,19,33,34]. Using murine BMDCs and radiolabeled serine, we investigated the effects of myriocin (20 mM, 8 h) and allergen exposure (HDM, 30 mg/mL, 8 h) on the de novo ceramide pathway ( Fig.…”