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 the CD226-NECTIN2 T cell-cholangiocyte interaction as a key feature in bile duct inflammation in NOD.c3c4 mice and human liver disease.

• Why it matters: Understanding the cellular interactions underlying bile duct inflammation is crucial for developing targeted treatments for PSC and PBC, which currently lack effective therapies and have unclear pathogenic mechanisms.
• What they did: Researchers analyzed livers from 10, 20, and 40-week-old NOD.c3c4 mice using spatial transcriptomics and scRNA-seq, focusing on T cell-related interactions, and validated the CD226-NECTIN2 interaction through co-culture experiments, antibody treatments, and human tissue analysis.
• The result: The CD226-NECTIN2 interaction was identified, functionally validated, and observed in human diseased livers, suggesting it as a potential future therapeutic target for bile duct inflammatory diseases.