Japan Digestive Disease Week 2025
International Poster Session13 (JDDW)
October 31, 15:20–16:00, Room 15 (Kobe International Exhibition Hall No.1 Building Digital Poster Venue)
IP-65_G
Regulatory T cell stability influence bile duct regeneration during cholangitis Travel Award
- 1
- Centre for Inflammation Research, University of Edinburgh
- 2
- Department of Immunology and Immunotherapy, University of Birmingham
- 3
- Division of Gastroenterology & Hepatology, Graduate School of Medical and Dental Sciences, Niigata University
- 4
- Department of Gastroenterology, Faculty of Medicine, University of Yamanashi
Cholangiopathies such as Primary Sclerosing Cholangitis (PSC) cause damage to the bile ducts and fibrosis with no effective cure. Regulatory T cells (Tregs) numbers and function are impaired during PSC. It is unclear whether the defect in Tregs affects bile duct regeneration. We investigate whether Tregs regulate bile duct regeneration and the dynamics of Tregs turnover during bile duct injury.
We used transgenic model to mimic reduced Tregs infiltration during bile duct injury and showed that reduced intrahepatic Tregs limits bile duct regeneration. Fate mapping of Tregs showed that Tregs acquire a pro-inflammatory phenotype during injury, even after IL2 mediated Tregs expansion, highlighting the limitations of IL2 based therapy for liver. Ox40L upregulation in PSC patients correlates with fibrosis level. In mouse model of experimental cholangiopathy, combining IL2-complex administration and blocking Ox40L improves Treg stability and numbers, decreases periportal fibrosis and promote regeneration.
In summary, Tregs mediate cholangiocyte regeneration. Enhancing Treg numbers through IL2 complex administration and blocking Ox40 signalling simultaneously suppress the inflammatory phenotype of Tregs and reduces bile duct damage and fibrosis.
We used transgenic model to mimic reduced Tregs infiltration during bile duct injury and showed that reduced intrahepatic Tregs limits bile duct regeneration. Fate mapping of Tregs showed that Tregs acquire a pro-inflammatory phenotype during injury, even after IL2 mediated Tregs expansion, highlighting the limitations of IL2 based therapy for liver. Ox40L upregulation in PSC patients correlates with fibrosis level. In mouse model of experimental cholangiopathy, combining IL2-complex administration and blocking Ox40L improves Treg stability and numbers, decreases periportal fibrosis and promote regeneration.
In summary, Tregs mediate cholangiocyte regeneration. Enhancing Treg numbers through IL2 complex administration and blocking Ox40 signalling simultaneously suppress the inflammatory phenotype of Tregs and reduces bile duct damage and fibrosis.
- Index Term 1: Liver stem cell regeneration
- Index Term 2: Regulatory T cells