Role of liver-infiltrating CD3(+)CD56(+) natural killer T cells in the pathogenesis of nonalcoholic fatty liver disease

Background/Aims Natural killer T (NKT) cells have been recently reported to concern with various lipid disorders. The role of NKT cells in the hepatic lipid disorder, nonalcoholic fatty liver disease (NAFLD), has, however, not yet been clarified. To assess the role of NKT cells in the pathogenesis of NAFLD, we analyzed the composition and function of liver-infiltrating cells isolated from liver biopsy specimens of patients with NAFLD. Methods Specimens from 62 patients with NAFLD were studied, and 54 specimens among them reacted immunohistochemically with monoclonal antibodies against various surface markers. Moreover, using flow cytometry, we analyzed surface markers and intracytoplasmic cytokines of intrahepatic CD3(+)CD56(+) cells in 12 patients among them. Results Among the various populations of liver-infiltrating cells, only the numbers of CD56(+) cells were significantly increased as NAFLD disease activity (NAFLD activity score, NAS) increased. Furthermore, expression of CD1d, a ligand for NKT cells, was also increased in NAFLD as NAS increased. Flow cytometric analysis showed that most CD56(+) cells were V alpha 24(+) NKT cells, which produced more IFN-gamma and IL-4 as NAS increased. Conclusion Intrallepatic CD3(+)CD56(+) NKT cells are increased in NAFLD as NAS increased. These cells may enhance disease activity through cytokine production after the recognition of lipid antigens presented with CD1d in livers of NAFLD. Eur J Gastroenterol Hepatol 21:673-680 (c) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.