Fas engagement induces the maturation of dendritic cells (DCs), the release of interleukin (IL)-1beta, and the production of interferon gamma in the absence of IL-12 during DC-T cell cognate interaction: a new role for Fas ligand in inflammatory responses
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State: Public
Version: author
State: Public
Version: author
Serval ID
serval:BIB_5E46822A3EE4
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Fas engagement induces the maturation of dendritic cells (DCs), the release of interleukin (IL)-1beta, and the production of interferon gamma in the absence of IL-12 during DC-T cell cognate interaction: a new role for Fas ligand in inflammatory responses
Journal
Journal of Experimental Medicine
ISSN
0022-1007 (Print)
Publication state
Published
Issued date
12/2000
Volume
192
Number
11
Pages
1661-8
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Dec 4
Research Support, Non-U.S. Gov't --- Old month value: Dec 4
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-1beta-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)-1beta and tumor necrosis factor alpha. Mature DCs, if exposed to FasL, produce even higher amounts of IL-1beta. Importantly, it is possible to reduce the production of IL-1beta and interferon (IFN)-gamma 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-gamma secretion is independent of IL-12.
Keywords
Antigens, CD95/*immunology
Apoptosis/drug effects
CASP8 and FADD-Like Apoptosis Regulating Protein
Carrier Proteins/biosynthesis
Cell Differentiation
Cells, Cultured
Dendritic Cells/cytology/drug effects/*immunology
Fas Ligand Protein
Humans
Inflammation/*immunology
Interferon Type II/*biosynthesis
Interleukin-1/*metabolism
Interleukin-12/*immunology
*Intracellular Signaling Peptides and Proteins
Lipopolysaccharides/pharmacology
Membrane Glycoproteins/*immunology
Mitogens/pharmacology
Phenotype
T-Lymphocytes/*immunology
Tumor Necrosis Factor-alpha/pharmacology
Up-Regulation/drug effects
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 16:19
Last modification date
20/08/2019 15:16