ArticleJHEP reports : innovation in hepatology2026
Intrahepatic T cell analysis reveals Th17 and MAIT17 enrichment in primary sclerosing cholangitis.
Article in JHEP reports : innovation in hepatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Focus on Mucosal-Associated Invariant T Cell Antigens Fueling Biliary Liver Injury.Cellular and molecular gastroenterology and hepatology · 2026Article
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14 authors.
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Abstract
BACKGROUND &
aimsPrimary sclerosing cholangitis (PSC) is an immune-mediated liver disease where the exact contribution of T cells is unclear. To deeply characterize intrahepatic T cells in PSC, we combined single-cell RNA sequencing (scRNA-seq) with T cell receptor sequencing (TCR-seq) and functional confirmation, using primary biliary cholangitis (PBC) and alcohol-related liver disease (ALD) as disease controls.
methodsIntrahepatic T cells from 12 PSC, nine PBC and three ALD explants were enriched by negative selection, viability-sorted and analyzed by scRNA-seq for total gene and TCR expression. T helper 17 (Th17) and IL-17
resultsScRNA-seq of 40,897 intrahepatic T cells revealed increased Th17/MAIT17 proportions in PSC livers compared with PBC (1.9-fold) and ALD (3.5-fold). Liver Th17 and MAIT17 expressed tissue-resident markers (CD69, CXCR6, ITGAE) and relative abundances measured by scRNA-seq correlated with proportions detected by flow cytometry. Immunohistochemistry liver staining of a validation cohort (n = 37) showed higher fractions of RORγt
conclusionsMultimodal analysis of intrahepatic T cells in PSC revealed a novel enrichment of Th17 and MAIT17 which may reflect increased IL-17 polarization of T cells within the PSC microenvironment. IMPACT AND IMPLICATIONS: PSC is a progressive cholestatic biliary disease featuring liver T cell infiltration of unknown significance. To better define the role of T cells in PSC, we phenotyped intrahepatic T cells by scRNA-seq and detected increased proportions of tissue-resident Th17 and MAIT17 cells in PSC relative to disease controls. TCR sequencing also revealed that liver Th17 and MAIT17 TCR clonotypes were more frequent in blood from individuals with PSC compared with PBC. Collectively our results suggest that PSC is associated with a greater expansion of liver Th17 and MAIT17 which may contribute to the pathogenesis of PSC.
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