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

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-1? family cytokines require proteolysis to gain biological activity. Inflammasomes, which respond to pathogens and danger signals, cleave IL-1? cytokines via caspase-1. However, the mechanisms by which Fas regulates IL-1? 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-1? and IL-18 independently of inflammasomes or RIP3. Hence, Fas controls a novel noncanonical IL-1? activation pathway in myeloid cells, which could play an essential role in inflammatory processes, tumor surveillance, and control of infectious diseases.

SUBMITTER: Bossaller L 

PROVIDER: S-EPMC3518757 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature