Mucosal-associated invariant T cells drive bile duct inflammation.

BACKGROUND & AIMS: Mucosal-associated invariant T (MAIT) cells recognize microbial-derived vitamin B metabolites presented by MR1. Since bile from patients with chronic biliary inflammation contain MAIT antigens, we investigated whether intrabiliary MAIT antigen exposure activates MAIT cells and induce pathogenic biliary inflammation. METHODS: Tg mice demonstrated antigen-driven transcriptional reprogramming toward a MAIT17-skewed phenotype with enrichment of TCR signaling pathways. CONCLUSIONS: MAIT cells can drive pathogenic bile duct inflammation in vivo when locally exposed to antigens. These findings suggest that modulation of MAIT driven immune pathways may represent a therapeutic approach in inflammatory cholangiopathies.