Volume 23 Issue 8, August 2026

Cover caption: On the chessboard of macrophages in atherosclerosis, CCRL2 begins as a humble pawn, stationed on the macrophage surface and uninvolved in NLRP3 inflammasome activation. When danger signals arise, this pawn undergoes endocytosis, advancing to its queening square, the early endosome. There, the change in subcellular location rewrites its fate: CCRL2 is promoted to a queen that acts as a structural anchor, facilitating the assembly of NLRP3 and ASC into a blazing inflammasome orb. This fiery orb ignites caspase-1 and unleashes IL-1β, fanning the flames of plaque inflammation and propelling atherosclerosis progression. Our study uncovers that compartment-specific trafficking within macrophages transforms the pawn CCRL2 into a pathogenic queen wielding a fiery core. Targeting this promoted axis, rather than global signals, offers a precise strategy to smother the blaze and arrest disease progression.

Refer to: Macrophage CCRL2 Promotes NLRP3 Inflammasome Activation to Exacerbate Atherosclerosis. pp:958-971.