The role of liver CD1‐restricted NK T cells in a model of recurrent colitis

The liver contains a unique population of lymphocytes including variant NKT cells, which are postulated to play a role in ulcerative colitis. Our aim was to characterize the role of CD1‐restricted NKT cells in Dextran Sodium Sulfate (DSS)‐induced colitis as well as their effects on early liver fibrosis. Male C57B1/6 or B6CD1 − /‐(deficient in CD1‐restricted NK T cells) mice were exposed to three cycles of 4% (w/v) DSS in drinking water for 5 days with 16 days between each cycle. The hepatic microcirculation was examined by intravital microscopy at 7 days post DSS treatment. Blood was collected for leukocyte counts, liver chemistry and histological examination. C57Bl/6 mice, exposed to 3 cycles of DSS, displayed significant hepatic inflammation as well as histological and immunohistochemical evidence of early periportal fibrosis. DSS treated B6CD1 − /‐ mice displayed a 30‐fold decrease in the flux of rolling leukocytes in the hepatic central venules when compared to matched C57Bl/6 mice for treatment and time points (3.6±1.0 vs 30.7±1.3 cells/min/field of view). Similarly, there was a 10‐fold significant decrease in the number of adherent leukocytes (0.8±0.5 vs 10.7±1.7 cells/min/field of view). Interestingly, there was a significant decrease in the clinical, macroscopic colitis score in B6CD1 − /‐ mice compared to C57B1/6 mice, as well as a reduction in periportal fibrosis. In C57Bl/6 mice, exposed to recurrent cycles of DSS colitis develop severe hepatic inflammation, altered biliary function and early fibrosis. Mice deficient in CD1 restricted NKT cells are protected from the DSS‐induced colonic and hepatic pathology. This suggests an important role for NKT cells in the pathogenesis of the DSS‐induced colitis and its associated extraintestinal manifestations. This work was supported by a Canadian Liver Foundation summer studentship.