| Autor: |
Kevin De Muynck, Bart Vanderborght, Federico F. De Ponti, Eva Gijbels, Sophie Van Welden, Martin Guilliams, Charlotte L. Scott, Alain Beschin, Mathieu Vinken, Sander Lefere, Anja Geerts, Xavier Verhelst, Hans Van Vlierberghe, Lindsey Devisscher |
| Přispěvatelé: |
Faculty of Law and Criminology, Brussels Heritage Lab, Clinical Biology, Department of Bio-engineering Sciences, Pharmaceutical and Pharmacological Sciences, Experimental in vitro toxicology and dermato-cosmetology |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| DOI: |
10.1016/j.ajpath.2022.12.008 |
| Popis: |
Primary sclerosing cholangitis (PSC) is an idiopathic chronic immune-mediated cholestatic liver disease characterized by fibro-inflammatory bile duct strictures, progressive hepatobiliary fibrosis, and gut-liver axis disruption. The pathophysiology of PSC remains insufficiently characterized, which hampers the development of effective therapies. Hepatic macrophages (MFs) such as Kupffer cells (KCs) are implicated in PSC pathogenesis, but their exact role is unclear. Using the latest markers to discriminate resident KCs (ResKCs) from their monocyte-derived counterparts (MoKCs), and two models of intrahepatic and extrahepatic cholestasis, respectively, this study showed that CLEC4F+TIM4+ ResKCs were depleted after chronic cholestatic liver injury. The infiltrating CLEC4F+TIM4- MoKCs were already enriched during the acute phase of PSC. Transcriptional profiling of hepatic MF subsets during early cholestatic injury indicated that ResKCs were indeed activated and that MoKCs expressed higher levels of pro-inflammatory and proliferative markers compared with those of ResKCs. As indicated in experiments with Clec4fDTR transgenic mice, conditional depletion of KCs, before and during early cholestasis induction, had no effect on the composition of the hepatic myeloid cell pool following injury progression and did not affect disease outcomes. Taken together, these results provide new insights into the heterogeneity of the MF pool during experimental PSC and evidence that depletion of resident and activated KCs during sclerosing cholangitis does not affect disease outcome in mice. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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