*Department of Immunology, Istituto Superiore di Sanità, viale Regina Elena 299, 00161 Rome and #Department of Experimental Medicine and Biochemical Sciences, University of Tor Vergata, via di Tor Vergata 135, 00133 Rome, Italy.

Corresponding author: Roberto Testi

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, utilize 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 TNFalpha and IL-1beta, 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 APC function and antigen-specific immune responses.