Abstract

Patients with psoriasis have an increased risk of developing inflammatory bowel disease, yet the mechanisms underlying this comorbidity remain unclear. In a clinical cohort, we observed an inverse correlation between psoriasis severity and postprandial plasma apolipoprotein B48 levels, a finding recapitulated in experimental psoriasis mouse models, indicating impaired intestinal lipid handling. To directly interrogate this process, we developed a recombinant photoconvertible apolipoprotein B reporter that enables real-time quantification of endogenous chylomicron production in intestinal organoids and in vivo . Using this system, we demonstrate that psoriasis promotes the expansion of interleukin (IL)-1β-producing intestinal macrophages, which accelerate apolipoprotein B degradation, impair chylomicron secretion, drive epithelial lipid accumulation, and exacerbate mucosal inflammation. Integrating human and experimental data, our findings implicate macrophage-driven metabolic dysregulation of the intestinal epithelium as a mechanistic link between psoriasis and gut inflammation and highlight intestinal IL-1β as a potential therapeutic target.