Cutting edge
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Cutting edge : FAS (CD95) mediates noncanonical IL-1β and IL-18 maturation via caspase-8 in an RIP3-independent manner. / Bossaller, Lukas; Chiang, Ping-I; Schmidt-Lauber, Christian; Ganesan, Sandhya; Kaiser, William J; Rathinam, Vijay A K; Mocarski, Edward S; Subramanian, Deepa; Green, Douglas R; Silverman, Neal; Fitzgerald, Katherine A; Marshak-Rothstein, Ann; Latz, Eicke.
In: J IMMUNOL, Vol. 189, No. 12, 15.12.2012, p. 5508-12.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Cutting edge
T2 - FAS (CD95) mediates noncanonical IL-1β and IL-18 maturation via caspase-8 in an RIP3-independent manner
AU - Bossaller, Lukas
AU - Chiang, Ping-I
AU - Schmidt-Lauber, Christian
AU - Ganesan, Sandhya
AU - Kaiser, William J
AU - Rathinam, Vijay A K
AU - Mocarski, Edward S
AU - Subramanian, Deepa
AU - Green, Douglas R
AU - Silverman, Neal
AU - Fitzgerald, Katherine A
AU - Marshak-Rothstein, Ann
AU - Latz, Eicke
PY - 2012/12/15
Y1 - 2012/12/15
N2 - 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-1β family cytokines require proteolysis to gain biological activity. Inflammasomes, which respond to pathogens and danger signals, cleave IL-1β cytokines via caspase-1. However, the mechanisms by which Fas regulates IL-1β 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-1β and IL-18 independently of inflammasomes or RIP3. Hence, Fas controls a novel noncanonical IL-1β activation pathway in myeloid cells, which could play an essential role in inflammatory processes, tumor surveillance, and control of infectious diseases.
AB - 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-1β family cytokines require proteolysis to gain biological activity. Inflammasomes, which respond to pathogens and danger signals, cleave IL-1β cytokines via caspase-1. However, the mechanisms by which Fas regulates IL-1β 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-1β and IL-18 independently of inflammasomes or RIP3. Hence, Fas controls a novel noncanonical IL-1β activation pathway in myeloid cells, which could play an essential role in inflammatory processes, tumor surveillance, and control of infectious diseases.
KW - Animals
KW - Caspase 8/genetics
KW - Dendritic Cells/enzymology
KW - Enzyme Activation/immunology
KW - Fas-Associated Death Domain Protein/deficiency
KW - Inflammasomes/metabolism
KW - Interleukin-18/biosynthesis
KW - Interleukin-1beta/biosynthesis
KW - Macrophages, Peritoneal/enzymology
KW - Mice
KW - Mice, Inbred BALB C
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Mice, Transgenic
KW - Receptor-Interacting Protein Serine-Threonine Kinases/deficiency
KW - Signal Transduction/genetics
KW - fas Receptor/physiology
U2 - 10.4049/jimmunol.1202121
DO - 10.4049/jimmunol.1202121
M3 - SCORING: Journal article
C2 - 23144495
VL - 189
SP - 5508
EP - 5512
JO - J IMMUNOL
JF - J IMMUNOL
SN - 0022-1767
IS - 12
ER -