Temporal assessment of spatial and single-cell transcriptomes identifies CD226-NECTIN2 T cell-cholangiocyte interaction in bile duct inflammation.

Spatial and single-cell transcriptomics reveal CD226-NECTIN2 T cell-cholangiocyte interaction as a key factor in bile duct inflammation in mouse and human liver disease.

• Why it matters: Understanding the cellular interactions driving bile duct inflammation is crucial for developing targeted therapies for PSC and PBC, diseases with limited treatment options and unclear mechanisms.
• What they did: The study used spatial transcriptomics and scRNA-seq on NOD.c3c4 mice at multiple ages, combined with validation in human liver samples, to identify and validate the CD226-NECTIN2 interaction involved in disease progression.
• The result: Disruption of this interaction reduced T cell activation and was consistently observed in inflamed human bile ducts, suggesting it as a promising target for future therapeutic intervention.