Ceramide inhibits antigen uptake and presentation by dendritic cells.
Ceramides are intramembrane diffusible mediators involved in transducing signals originated from a variety of cell surface receptors. Different adaptive and differentiative cellular responses, including apoptotic cell death, use ceramide-mediated pathways as an essential part of the program. Here, we show that human dendritic cells respond to CD40 ligand, as well as to tumor necrosis factor-alpha and IL-1 beta, with intracellular ceramide accumulation, as they are induced to differentiate. Dendritic cells down-modulate their capacity to take up soluble antigens in response to exogenously added or endogenously produced ceramides. This is followed by an impairment in presenting soluble antigens to specific T cell clones, while cell viability and the capacity to stimulate allogeneic responses or to present immunogenic peptides is fully preserved. Thus, ceramide-mediated pathways initiated by different cytokines can actively modulate professional antigen-presenting cell function and antigen-specific immune responses.
Sallusto
F
F
Department of Immunology, Istituto Superiore di Sanità, Rome, Italy.
Nicolò
C
C
De Maria
R
R
Corinti
S
S
Testi
R
R
D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000378:metabolism*; D001692:Biological Transport; D023201:CD40 Ligand; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured; D002518:Ceramides / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004705:Endocytosis / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000941:Antigens; D002518:Ceramides; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand