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- Title
CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer.
- Authors
Stewart, Cameron R.; Stuart, Lynda M.; Wilkinson, Kim; van Gils, Janine M.; Jiusheng Deng; Halle, Annett; Rayner, Katey J.; Boyer, Laurent; Ruiqin Zhong; Frazier, William A.; Lacy-Hulbert, Adam; Khoury, Joseph El; Golenbock, Douglas T.; Moore, Kathryn J.
- Abstract
In atherosclerosis and Alzheimer's disease, deposition of the altered self components oxidized low-density lipoprotein (LDL) and amyloid-β triggers a protracted sterile inflammatory response. Although chronic stimulation of the innate immune system is believed to underlie the pathology of these diseases, the molecular mechanisms of activation remain unclear. Here we show that oxidized LDL and amyloid-β trigger inflammatory signaling through a heterodimer of Toll-like receptors 4 and 6. Assembly of this newly identified heterodimer is regulated by signals from the scavenger receptor CD36, a common receptor for these disparate ligands. Our results identify CD36-TLR4-TLR6 activation as a common molecular mechanism by which atherogenic lipids and amyloid-β stimulate sterile inflammation and suggest a new model of TLR heterodimerization triggered by coreceptor signaling events.
- Subjects
ALZHEIMER'S disease; ATHEROSCLEROSIS; GLYCOPROTEINS; LOW density lipoproteins; IMMUNE system
- Publication
Nature Immunology, 2010, Vol 11, Issue 2, p155
- ISSN
1529-2908
- Publication type
Article
- DOI
10.1038/ni.1836