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- Title
TRAM is specifically involved in the Toll-like receptor 4-mediated MyD88-independent signaling pathway.
- Authors
Yamamoto, Masahiro; Sato, Shintaro; Hemmi, Hiroaki; Uematsu, Satoshi; Hoshino, Katsuaki; Kaisho, Tsuneyasu; Takeuchi, Osamu; Takeda, Kiyoshi; Akira, Shizuo
- Abstract
Recognition of pathogens by Toll-like receptors (TLRs) triggers innate immune responses through signaling pathways mediated by Toll-interleukin 1 receptor (TIR) domain-containing adaptors such as MyD88, TIRAP and TRIF. MyD88 is a common adaptor that is essential for proinflammatory cytokine production, whereas TRIF mediates the MyD88-independent pathway from TLR3 and TLR4. Here we have identified a fourth TIR domain-containing adaptor, TRIF-related adaptor molecule (TRAM), and analyzed its physiological function by gene targeting. TRAM-deficient mice showed defects in cytokine production in response to the TLR4 ligand, but not to other TLR ligands. TLR4- but not TLR3-mediated MyD88-independent interferon-beta production and activation of signaling cascades were abolished in TRAM-deficient cells. Thus, TRAM provides specificity for the MyD88-independent component of TLR4 signaling.
- Publication
Nature immunology, 2003, Vol 4, Issue 11, p1144
- ISSN
1529-2908
- Publication type
Journal Article
- DOI
10.1038/ni986