NDLI: Cutting edge: FAS (CD95) mediates noncanonical IL-1ß and IL-18 maturation via caspase-8 in an RIP3-independent manner.

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Cutting edge: FAS (CD95) mediates noncanonical IL-1ß and IL-18 maturation via caspase-8 in an RIP3-independent manner.

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Cutting edge: FAS (CD95) mediates noncanonical IL-1ß and IL-18 maturation via caspase-8 in an RIP3-independent manner.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Ganesan, Sandhya Bossaller, Lukas Chiang, Ping-I Green, Douglas R. Marshak-Rothstein, Ann Silverman, Neal Kaiser, William J. Schmidt-Lauber, Christian Subramanian, Deepa Rathinam, Vijay A. K. Fitzgerald, Katherine A. Mocarski, Edward S. Latz, Eicke
Description	Country affiliation: United States Author Affiliation: Bossaller L ( Department of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA.)
Abstract	Fas, a TNF family receptor, is activated by the membrane protein Fas ligand expressed on various immune cells. Fas signaling triggers apoptosis and induces inflammatory cytokine production. Among the Fas-induced cytokines, the IL-1ß family cytokines require proteolysis to gain biological activity. Inflammasomes, which respond to pathogens and danger signals, cleave IL-1ß cytokines via caspase-1. However, the mechanisms by which Fas regulates IL-1ß activation remain unresolved. In this article, we demonstrate that macrophages exposed to TLR ligands upregulate Fas, which renders them responsive to receptor engagement by Fas ligand. Fas signaling activates caspase-8 in macrophages and dendritic cells, leading to the maturation of IL-1ß and IL-18 independently of inflammasomes or RIP3. Hence, Fas controls a novel noncanonical IL-1ß activation pathway in myeloid cells, which could play an essential role in inflammatory processes, tumor surveillance, and control of infectious diseases.
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1202121
Journal	The Journal of Immunology
Issue Number	12
Volume Number	189
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2012-12-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Antigens, Cd95 Physiology Caspase 8 Interleukin-18 Biosynthesis Interleukin-1beta Receptor-interacting Protein Serine-threonine Kinases Animals Genetics Metabolism Dendritic Cells Enzymology Immunology Enzyme Activation Fas-associated Death Domain Protein Deficiency Inflammasomes Macrophages, Peritoneal Mice Mice, Inbred Balb C Mice, Inbred C57bl Mice, Knockout Mice, Transgenic Signal Transduction Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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