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Fas Engagement Induces the Maturation of Dendritic Cells (DCs), the Release of Interleukin (IL)-1ß, and the Production of Interferon in the Absence of IL-12 during DC–T Cell Cognate Interaction: A New Role for Fas Ligand in Inflammatory Responses

Correspondence to: Paola Ricciardi-Castagnoli, Department of Biotechnology and Bioscience, University of Milano-Bicocca, 20126 Milan, Italy. Tel:39-02-644-83559 Fax:39-02-644-83565 E-mail:paola.castagnoli{at}unimib.it.

Ligation of the Fas (CD95) receptor leads to an apoptotic death signal in T cells, B cells, and macrophages. However, human CD34⁺–derived dendritic cells (DCs) and mouse DCs, regardless of their maturation state, are not susceptible to Fas-induced cell death. This resistance correlates with the constitutive expression of the Fas-associated death domain–like IL-1ß–converting enzyme (FLICE)-inhibitory protein (FLIP) ligand. We demonstrate a new role of Fas in DC physiology. Engagement of Fas on immature DCs by Fas ligand (FasL) or by anti-Fas antibodies induces the phenotypical and functional maturation of primary DCs. Fas-activated DCs upregulate the expression of the major histocompatibility complex class II, B7, and DC–lysosome-associated membrane protein (DC-LAMP) molecules and secrete proinflammatory cytokines, in particular interleukin (IL)-1ß and tumor necrosis factor . Mature DCs, if exposed to FasL, produce even higher amounts of IL-1ß. Importantly, it is possible to reduce the production of IL-1ß and interferon (IFN)- during DC–T cell interaction by blocking the coupling of Fas–FasL with a Fas competitor. Finally, during cognate DC–T cell recognition, IL-12 (p70) could not be detected at early or late time points, indicating that Fas-induced, IFN- secretion is independent of IL-12.

Key Words: dendritic cells, Fas, interleukin 1ß, FLIP, interferon

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