Colonic ATP administration to Mdr2–/– mice recapitulates the liver phenotype of Mdr2–/–;CD39–/– mice. Stable ATP agonist (αβ‐ATP, 1 mg/kg/day) or vehicle (RPMI medium) was rectally administered into 5‐week‐old male Mdr2–/– mice daily for 6 days. (A) Double immunofluorescence for CD8+ (red) and biliary marker p‐CK (green) showed remarkable CD8+ T‐cell (arrowheads) infiltration in portal areas in Mdr2–/– mice challenged with αβ‐ATP (original magnification, ×200). (B) CD8+ T cells were quantified by counting 10 randomly selected high‐power fields and by measuring hepatic CD8 mRNA expression. (C) Elevation of serum ALT and ALP in mice treated with αβ‐ATP. (D) mRNA expression of Col1a1, Tgfb2, as well as the gut‐homing markers Itgb7, Ccr9 (n.s.). Data are mean ± SEM (n = 3 mice/bar). *P < 0.05 compared to vehicle‐treated Mdr2–/– (t test). Abbreviations: HPF, high‐power field; Itgb7, integrin b7; n.s., not significant; p‐CK, pan‐cytokeratine; RPMI, Roswell Park Memorial Institute; Tgfb2, transforming growth factor β2.