Osteopontin characterizes bile duct–associated macrophages and correlates with liver fibrosis severity in primary sclerosing cholangitis
Kevin De Muynck, Lander Heyerick, Federico F. De Ponti, Bart Vanderborght, Tim Meese, Sanne Van Campenhout, Leen Baudonck, Eva Gijbels, Pedro M. Rodrigues, Jesus M. Banales, Mette Vesterhuus, Trine Folseraas, Charlotte L. Scott, Mathieu Vinken, Malaïka Van der Linden, Anne Hoorens, Jo Van Dorpe, Sander Lefere, Anja Geerts, Filip Van Nieuwerburgh, Xavier Verhelst, Hans Van Vlierberghe, Lindsey Devisscher- Hepatology
Background and Aims:
Primary sclerosing cholangitis (PSC) is an immune-mediated cholestatic liver disease for which pharmacological treatment options are currently unavailable. PSC is strongly associated with colitis and a disruption of the gut-liver axis, and macrophages are involved in the pathogenesis of PSC. However, how gut-liver interactions and specific macrophage populations contribute to PSC is incompletely understood.
Approach and Results:
We investigated the impact of cholestasis and colitis on the hepatic and colonic microenvironment, and performed an in-depth characterization of hepatic macrophage dynamics and function in models of concomitant cholangitis and colitis. Cholestasis-induced fibrosis was characterized by depletion of resident KCs, and enrichment of monocytes and monocyte-derived macrophages (MoMFs) in the liver. These MoMFs highly express triggering-receptor-expressed-on-myeloid-cells-2 (
Conclusions:
Our data shed light on gut-liver axis perturbations and macrophage dynamics and function in PSC and highlight SPP1/OPN as a prognostic marker and future therapeutic target in PSC.