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Publication : CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer.

First Author  Stewart CR Year  2010
Journal  Nat Immunol Volume  11
Issue  2 Pages  155-61
PubMed ID  20037584 Mgi Jnum  J:158401
Mgi Id  MGI:4438693 Doi  10.1038/ni.1836
Citation  Stewart CR, et al. (2010) CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer. Nat Immunol 11(2):155-61
abstractText  In atherosclerosis and Alzheimer's disease, deposition of the altered self components oxidized low-density lipoprotein (LDL) and amyloid-beta 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-beta 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-beta stimulate sterile inflammation and suggest a new model of TLR heterodimerization triggered by coreceptor signaling events.
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