Role of liver-infiltrating CD3+CD56+ natural killer T cells ... : European Journal of Gastroenterology & Hepatology (original) (raw)

Original Articles: Fatty Liver Disease

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

Tajiri, Kazutoa; Shimizu, Yukihiroc; Tsuneyama, Koichib; Sugiyama, Toshiroa

aDepartment of Gastroenterology and Hematology

bFirst Department of Pathology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama

cCenter for Gastroenterology and Hepatology, Kyoto Katsura Hospital, Kyoto, Japan

Correspondence to Yukihiro Shimizu, MD, PhD, Center for Gastroenterology and Hepatology, Kyoto Katsura Hospital, 17 Yamada-Hirao, Nishikyo-ku, Kyoto 615-8256, Japan

Tel: +81 75 391 5811; fax: +81 75 381 0090; e-mail: [email protected]

Received 27 August 2008 Accepted 2 October 2008

European Journal of Gastroenterology & Hepatology 21(6):p 673-680, June 2009. | DOI: 10.1097/MEG.0b013e32831bc3d6

Abstract

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 Vα24+ NKT cells, which produced more IFN-γ and IL-4 as NAS increased.

Conclusion

Intrahepatic 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.