2. Academic Validation
  3. Psoriasis modulates inflammatory bowel disease risk and intestinal epithelium lipid metabolism via IL-1β-producing macrophages

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.
Jiaqi Wu 1,  Shuangshuang Liu 1,  Wei Dan 1,  Xiao Tong 1,  Jingyi Gong 1,  Zimeng Li 1,  Yu Gu 1,  Jindian Xu 2,  Weiwei Chen 2,  Shupei Wang 1,  Xue-Yang Luo 1,  Huanya Yang 1,  Yingli Jia 1,  Chih-Hao Chang 3,  Kexiang Yan 4,  Jiaxi Wang 5,  Li-Hao Huang 6
Affiliations

Affiliations

  • 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].
PMID: 41856104 DOI: 10.1016/j.cmet.2026.02.014
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.

Keywords

apolipoprotein B48; chylomicron; inflammatory bowel disease; macrophages; photoconversion; psoriasis.

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