CD36 coordinates NLRP3 inflammasome activation by facilitating the intracellular nucleation from soluble to particulate ligands in sterile inflammation

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CD36 coordinates NLRP3 inflammasome activation by facilitating the intracellular nucleation from soluble to particulate ligands in sterile inflammation

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Title: CD36 coordinates NLRP3 inflammasome activation by facilitating the intracellular nucleation from soluble to particulate ligands in sterile inflammation
Author: Sheedy, Frederick J.; Grebe, Alena; Rayner, Katey J.; Kalantari, Parisa; Ramkhelawon, Bhama; Carpenter, Susan B.; Becker, Christine E.; Ediriweera, Hasini N.; Mullick, Adam E.; Golenbock, Douglas T.; Stuart, Lynda M.; Latz, Eicke; Fitzgerald, Katherine A.; Moore, Kathryn J.

Note: Order does not necessarily reflect citation order of authors.

Citation: Sheedy, F. J., A. Grebe, K. J. Rayner, P. Kalantari, B. Ramkhelawon, S. B. Carpenter, C. E. Becker, et al. 2013. “CD36 coordinates NLRP3 inflammasome activation by facilitating the intracellular nucleation from soluble to particulate ligands in sterile inflammation.” Nature immunology 14 (8): 812-820. doi:10.1038/ni.2639. http://dx.doi.org/10.1038/ni.2639.
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Abstract: Particulate ligands including cholesterol crystals and amyloid fibrils induce NLRP3-dependent production of interleukin-1β (IL-1β) in atherosclerosis, Alzheimer's disease and diabetes. Soluble endogenous ligands including oxidized-LDL, amyloid-β and amylin peptides accumulate in these diseases. Here we identify a CD36-mediated endocytic pathway that coordinates the intracellular conversion of these soluble ligands to crystals or fibrils, resulting in lysosomal disruption and NLRP3-inflammasome activation. Consequently, macrophages lacking CD36 failed to elicit IL-1β production in response to these ligands and targeting CD36 in atherosclerotic mice reduced serum IL-1β and plaque cholesterol crystal accumulation. Collectively, these findings highlight the importance of CD36 in the accrual and nucleation of NLRP3 ligands from within the macrophage and position CD36 as a central regulator of inflammasome activation in sterile inflammation.
Published Version: doi:10.1038/ni.2639
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3720827/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:11879825
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