Mechanism of Interleukin-1/Toll-like receptor signaling mediated macrophage atherosclerosis
The role of and mechanism(s) by which interleukin-1 receptor type 1 (IL-1R1)/Toll-like receptor (TLR) signaling modulates the inflammasome response and resultant atherosclerosis remain unknown.
The researchers in this study demonstrate that IL-1R1/TLR signaling enhances atherosclerosis by disrupting β-arrestin-2 (βarr2)-mediated olfactory receptor (OR6A2) internalization in macrophages.
This shift, driven by βarr2K295 deSUMOylation-dependent TRAF6-βarr2 coupling, sustains NLRP3 inflammasome activation.
Targeting this pathway may offer therapeutic strategies to mitigate inflammation-driven vascular disease.
https://www.cell.com/cell-reports/fulltext/S2211-1247(25)01411-1
