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 Fasinduced 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 Fasinduced 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84871125002&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1202121
DO - 10.4049/jimmunol.1202121
M3 - Article
C2 - 23144495
AN - SCOPUS:84871125002
VL - 189
SP - 5508
EP - 5512
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 12
ER -