In:
The Journal of Immunology, The American Association of Immunologists, Vol. 189, No. 12 ( 2012-12-15), p. 5508-5512
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-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.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.1202121
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2012
detail.hit.zdb_id:
1475085-5
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