Psoriasis modulates inflammatory bowel disease risk and intestinal epithelium lipid metabolism via IL-1β-producing macrophages
- Cell Metab. 2026 May 5;38(5):963-980.e12. doi: 10.1016/j.cmet.2026.02.014.
- 1. Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism & Integrative Biology, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200438, China.
- 2. Center for Medical Research and Innovation, Shanghai Pudong Hospital, Human Phenome Institute, Zhangjiang-Fudan International Innovation Center, Fudan University, Shanghai 200438, China.
- 3. The Jackson Laboratory, Bar Harbor, ME 04609, USA.
- 4. Department of Dermatology, Huashan Hospital Affiliated to Fudan University, Shanghai 200040, China; Dermatology Department, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China. Electronic address: [email protected].
- 5. Center for Medical Research and Innovation, Shanghai Pudong Hospital, Human Phenome Institute, Zhangjiang-Fudan International Innovation Center, Fudan University, Shanghai 200438, China. Electronic address: [email protected].
- 6. Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism & Integrative Biology, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200438, China. Electronic address: [email protected].
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.