Fas engagement induces the maturation of dendritic cells (DCs), the release of interleukin (IL)-1β, and the production of interferon γ in the absence of IL-12 during DC-T cell cognate interaction: A new role for fas ligand in inflammatory responses

Maria Rescigno, Vincent Piguet, Barbara Valzasina, Suzanne Lens, Rudolf Zubler, Lars French, Vincent Kindler, Jurg Tschopp, Paola Ricciardi-Castagnoli

Research output: Contribution to journalArticle

Abstract

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-1β-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 DClysosome-associated membrane protein (DC-LAMP) molecules and secrete proinfiammatory cytokines, in particular interleukin (IL)-1β and tumor necrosis factor α. Mature DCs, if exposed to FasL, produce even higher amounts of IL-1β. Importantly, it is possible to reduce the production of IL-1β and interferon (IFN)-γ 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-γ secretion is independent of lL-12.

Original languageEnglish
Pages (from-to)1661-1668
Number of pages8
JournalJournal of Experimental Medicine
Volume192
Issue number11
DOIs
Publication statusPublished - Dec 4 2000

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Keywords

  • Dendritic cells
  • Fas
  • FLIP
  • Interferon γ
  • Interleukin 1β

ASJC Scopus subject areas

  • Immunology

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