Oleic acid suppresses NLRP3 inflammasome activation to prevent dermal macrophage death and limit imiquimod-induced psoriasis

Psoriasis is linked to irregular lipid metabolism, such as reduced fatty acid metabolism genes expression and lower circulating oleic acid levels. In a study using an imiquimod mouse model of psoriasis, oral oleic acid supplementation was found to restore serum oleic acid levels and prevent skin thickening and hyperplasia. This was linked to maintaining skin macrophage numbers and lowering key inflammatory markers associated with psoriasis.

Upon investigation, it was discovered that imiquimod triggers dermal macrophage death through NLRP3/caspase-1 inflammasome activation. However, transferring dermal macrophages from affected mice into healthy ones helped to reduce psoriasiform inflammation. In a laboratory setting, oleic acid was able to save macrophages from imiquimod and nigericin-induced death by suppressing NF-{kappa}B and NLRP3/caspase-1 signaling, reducing IL-1{beta} and reactive oxygen species production, and restoring mitochondrial balance, all of which were achieved independently of TLR7.

These findings suggest that maintaining dermal macrophage survival is a previously unexplored checkpoint in psoriasiform inflammation, and propose that enhancing lipid metabolic function, rather than just focusing on downstream inflammatory mediators, could serve as a novel strategy to curb tissue-damaging inflammation.