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Distinct macrophage subsets identified in pediatric cholestatic liver disease

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Three macrophage subsets with distinct transcriptional signatures were identified using single-cell RNA sequencing on the human pediatric cholestatic liver, according to a study.

Using live hepatic immune cells from patients with biliary atresia (BA), Alagille syndrome (ALGS), and non-cholestatic pediatric liver, researchers used single-cell RNA sequencing analysis and immunofluorescence to characterize cholestatic macrophages as lipid-associated macrophages, monocyte-like macrophages, and adaptive macrophages.

Compared to normal hepatic macrophages, cholestatic macrophages showed reduced expression of immune regulatory genes and were distinct from macrophage populations in healthy livers.

“Further analyses will identify similarities and differences in these macrophage sub-populations across etiologies of cholestatic liver disease,” the authors concluded. “Taken together, these findings may allow for future development of targeted therapeutic strategies to reprogram macrophages to an immune regulatory phenotype and reduce cholestatic liver injury.”

Taylor SA, Chen SY, Gadhvi G, et a. Transcriptional profiling of pediatric cholestatic livers identifies three distinct macrophage populations. PLoS One. 2021;16(1):e0244743. doi: 10.1371/journal.pone.0244743. PMID: 33411796; PMCID: PMC7790256.