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Updated: Jun 14, 2026
Characterization of Immune Cells and Proinflammatory Mediators in the Pulmonary Environment
Published on: June 24, 2020
Interleukin-8-driven monocyte activation in primary sclerosing cholangitis: Insights from single-cell analysis and
Lander Heyerick1, Zenzi De Vos2, Aline Baekelandt2
1Department of Basic & Applied Medical Sciences, Gut-Liver Immunopharmacology Unit, Ghent University, Ghent, Belgium; Liver Research Center Ghent, Ghent University, Ghent University Hospital, Ghent, Belgium; Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium.
Researchers identified a specific monocyte subset and intrahepatic macrophages contributing to primary sclerosing cholangitis (PSC) liver disease. Targeting the IL-8:CXCR1/2 pathway shows therapeutic promise for PSC patients.
Area of Science:
- Immunology
- Hepatology
- Translational Medicine
Background:
- Primary sclerosing cholangitis (PSC) is an immune-mediated liver disease with unknown causes.
- Monocyte and macrophage dysfunction is suspected in PSC pathogenesis but not fully understood.
- Humanized immune system (HIS) mouse models offer potential for studying human immune responses.
Purpose of the Study:
- Identify peripheral myeloid cell populations in PSC pathogenesis.
- Assess the therapeutic potential of targeting inflammatory signaling pathways.
- Utilize a HIS mouse model for enhanced translational relevance.
Main Methods:
- Profiled peripheral blood mononuclear cells from PSC patients, ulcerative colitis patients, and healthy controls using single-cell RNA sequencing.
- Evaluated IL-8:CXCR1/2 axis signaling in conventional and HIS mouse models of cholestatic liver disease.
Main Results:
- Identified a circulatory CXCL8+CD14+ monocyte subset with upregulated pro-inflammatory signaling in PSC patients.
- Increased serum IL-8 concentrations in PSC patients correlated with poor prognosis and worse transplant-free survival.
- Expanded intrahepatic IL-8+ macrophages were observed during PSC disease progression.
- Pharmacologic CXCR1 antagonism and IL-8 neutralization reduced cholestatic liver injury in mouse models.
Conclusions:
- A specific CXCL8+CD14+ monocyte subset and intrahepatic IL-8+ macrophages are implicated in PSC pathogenesis.
- HIS mouse models represent a significant advancement for translational research in human immune responses.
- Targeting the IL-8:CXCR1/2 axis presents a promising therapeutic strategy for PSC.
