A biliary immune landscape map of primary sclerosing cholangitis reveals a dominant network of neutrophils and tissue-resident T cells

Bile ducts from patients with PSC are enriched in neutrophils and biliary-resident CD8 + T cells and differ in composition from liver tissue. The human bile duct can often be a site of inflammation and disease, but the underlying immune landscape in the context of disease is not well understood. To address this, Zimmer et al. used endoscopy-guided sampling of the biliary tree in patients with primary sclerosing cholangitis (PSC) and non-PSC controls. The authors found that patients with PSC had the most prominent changes in the neutrophil and tissue-resident T cell populations in the bile duct. Together, this study provides a promising resource for understanding the immune landscape of the human bile duct. The human biliary system, a mucosal barrier tissue connecting the liver and intestine, is an organ often affected by serious inflammatory and malignant diseases. Although these diseases are linked to immunological processes, the biliary system represents an unexplored immunological niche. By combining endoscopy-guided sampling of the biliary tree with a high-dimensional analysis approach, comprehensive mapping of the human biliary immunological landscape in patients with primary sclerosing cholangitis (PSC), a severe biliary inflammatory disease, was conducted. Major differences in immune cell composition in bile ducts compared to blood were revealed. Furthermore, biliary inflammation in patients with PSC was characterized by high presence of neutrophils and T cells as compared to control individuals without PSC. The biliary T cells displayed a CD103 + CD69 + effector memory phenotype, a combined gut and liver homing profile, and produced interleukin-17 (IL-17) and IL-22. Biliary neutrophil infiltration in PSC associated with CXCL8, possibly produced by resident T cells, and CXCL16 was linked to the enrichment of T cells. This study uncovers the immunological niche of human bile ducts, defines a local immune network between neutrophils and biliary-resident T cells in PSC, and provides a resource for future studies of the immune responses in biliary disorders.