H M Kim1,2,7, B R Lee3,7, E S Lee2, M H Kwon2, J H Huh2, B-E Kwon3, E-K Park3, S-Y Chang4, M-N Kweon5, P-H Kim6, H-J Ko3,7,* and C H Chung1,2,7,*
1Department of Global Medical Science, Yonsei University Wonju College of Medicine, Wonju, Korea
2Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
3Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon, Korea
4College of Pharmacy, Ajou University, Suwon, Korea
5Mucosal Immunology Laboratory, Department of Convergence Medicine, University of Ulsan College of Medicine/Asan Medical Center, Seoul, Korea
6Department of Molecular Bioscience, School of Biomedical Science, Kangwon National University, Chuncheon, Korea
7These authors contributed equally to this work.
*Correspondence: Professor H-J Ko or Dr CH Chung
Abstract
Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis are characterized by an increase in hepatic triglyceride content with infiltration of immune cells, which can cause steatohepatitis and hepatic insulin resistance. C-C chemokine receptor 7 (CCR7) is primarily expressed in immune cells, and CCR7 deficiency leads to the development of multi-organ autoimmunity, chronic renal disease and autoimmune diabetes. Here, we investigated the effect of CCR7 on hepatic steatosis in a mouse model and its underlying mechanism. Our results demonstrated that body and liver weights were higher in the CCR7-/- mice than in the wild-type (WT) mice when they were fed a high-fat diet. Further, glucose tolerance and insulin sensitivity were markedly diminished in CCR7-/- mice. The number of invariant natural killer T (iNKT) cells was reduced in the livers of the CCR7-/- mice. Moreover, liver inflammation was detected in obese CCR7-/- mice, which was ameliorated by the adoptive transfer of hepatic mononuclear cells from WT mice, but not through the transfer of hepatic mononuclear cells from CD1d-/- or interleukin-10-deficient (IL-10-/-) mice. Overall, these results suggest that CCR7+ mononuclear cells in the liver could regulate obesity-induced hepatic steatosis via induction of IL-10-expressing iNKT cells.