Sheedy, Frederick J.Grebe, AlenaRayner, Katey J.Kalantari, ParisaRamkhelawon, BhamaCarpenter, Susan B.Becker, Christine E.Ediriweera, Hasini N.Mullick, Adam E.Golenbock, Douglas T.Stuart, LyndaLatz, EickeFitzgerald, Katherine A.Moore, Kathryn J.2014-03-112013Sheedy, 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.2639.1529-2908http://nrs.harvard.edu/urn-3:HUL.InstRepos:11879825Particulate 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.en-USJournal Article2014-03-1110.1038/ni.2639