Conserved ductular reaction mechanisms in biliary atresia and PSC derived from single-cell and spatial transcriptomics - PubMed
7 hours ago
- #primary sclerosing cholangitis
- #ductular reaction
- #biliary atresia
- The ductular reaction (DR) in both biliary atresia (BA) and primary sclerosing cholangitis (PSC) involves biliary ductules, immune infiltration, and fibroblast activation.
- Single-cell and spatial transcriptomics reveal conserved fibro-inflammatory mechanisms in the DR, including pro-fibrogenic hepatocyte-to-cholangiocyte transdifferentiation, cholangiocyte senescence, scar-/lipid-associated macrophage accumulation, Kupffer cell dysfunction, and portal fibroblast activation.
- Adaptive immune processes differ between BA and PSC, such as Th17 to Th1 transdifferentiation in BA, Th17 dominance in PSC, reduced CX3CR1 CD8/NKT-cells in BA, and gut-primed lymphocyte homing to the liver in PSC.
- Future research should include early- and late-stage disease samples (e.g., non-cirrhotic PSC) and utilize advanced spatial transcriptomic technologies to enhance prediction of ligand-receptor interactions.
- The findings support identifying therapeutic targets against conserved DR mechanisms applicable to multiple fibro-inflammatory disorders.