The role of natural killer T cells in a mouse model with spontaneous bile duct inflammation

摘要

Natural killer T (NKT) cells are activated by lipid antigens presented by CD1d molecules and represent a major lymphocyte subset of the liver. NOD.c3c4 mice spontaneously develop biliary inflammation in extra‐ and intrahepatic bile ducts. We demonstrated by flow cytometry that invariant NKT (iNKT) cells were more abundant in the thymus, spleen, and liver of NOD.c3c4 mice compared to NOD mice. iNKT cells in NOD.c3c4 mice displayed an activated phenotype. Further, NOD and NOD.Cd1d ^‐/‐ mice were irradiated and injected with NOD.c3c4 bone marrow, and injection of NOD.c3c4 bone marrow resulted in biliary infiltrates independently of CD1d expression in recipient mice. Activation or blocking of NKT cells with α‐galactosylceramide or anti‐CD1d antibody injections did not affect the biliary phenotype of style="fixed-case">NOD.c3c4 mice. style="fixed-case">NOD.c3c4.Cd1d ^‐/‐ mice were generated by crossing style="fixed-case">NOD.Cd1d ^‐/‐ mice onto a style="fixed-case">NOD.c3c4 background. style="fixed-case">NOD.c3c4.Cd1d ^‐/‐ and style="fixed-case">NOD.c3c4 mice developed the same extent of biliary disease. This study demonstrates that style="fixed-case">iNKT cells are more abundant and activated in the style="fixed-case">NOD.c3c4 model. The portal inflammation of style="fixed-case">NOD.c3c4 mice can be transferred to irradiated recipients, which suggests an immune‐driven disease. Our findings imply that style="fixed-case">NKT cells can potentially participate in the biliary inflammation, but are not the primary drivers of disease in style="fixed-case">NOD.c3c4 mice.