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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front. Med.    2018, Vol. 12 Issue (3) : 249-261
NKT cells in liver diseases
Shasha Zhu1,2, Huimin Zhang1,2, Li Bai1,2()
1. CAS Key Laboratory of Innate Immunity and Chronic Disease, CAS Center for Excellence in Molecular Cell Science, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei 230027, China
2. Innovation Center for Cell Signaling Network, Hefei National Laboratory for Physical Sciences at Microscale, Hefei 230027, China
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Natural killer T cells are innate-like and tissue-resident lymphocytes, which recognize lipid antigens and are enriched in the liver. Natural killer T cells play important roles in infections, tumors, autoimmune diseases, and metabolic diseases. In this study, we summarize recent findings on biology of natural killer T cells and their roles in hepatitis B virus and hepatitis C virus infection, autoimmune liver diseases, alcoholic liver disease, nonalcoholic fatty liver disease, and hepatocellular carcinoma. Controversial results from previous studies are discussed, and indicate the dynamic alteration in the role of natural killer T cells during the progression of liver diseases, which might be caused by changes in natural killer T subsets, factors skewing cytokine responses, and intercellular crosstalk between natural killer T cells and CD1d-expressing cells or bystander cells.

Keywords natural killer T cells      hepatitis B virus and hepatitis C virus infection      autoimmune liver diseases      alcoholic liver disease      nonalcoholic fatty liver disease      hepatocellular carcinoma     
Corresponding Authors: Li Bai   
Just Accepted Date: 09 February 2018   Online First Date: 09 April 2018    Issue Date: 04 May 2018
 Cite this article:   
Shasha Zhu,Huimin Zhang,Li Bai. NKT cells in liver diseases[J]. Front. Med., 2018, 12(3): 249-261.
Fig.1  Distribution of NKT cell subsets and their characteristics. NKT cells that emigrate from the thymus are mostly developed from a common precursor of CD4+CD8+ double-positive (DP) thymocytes. These double-positive precursors undergo a series of steps that ultimately results in the NKT cell pool with tissue-specific distribution. Hepatic and splenic NKT1 cells are IL-17RBT-bethighPLZFlow and secrete both IFN-γ and IL-4. The NKT2 defined as GATA3highPLZFhigh populations and NKT17 cells defined as RORγt+PLZFmed populations accumulate in the lung and lymph node, respectively, and both are IL-17RB+. In adipose tissues, NKT10 cells express the transcription factor E4BP4 and mainly secrete IL-10. Moreover, some CD4CD8 NKT cells are generated from CD4CD8 (double negative, DN) thymocytes and bypass the DP-stage. The CD4CD8 NKT cells of DN-stage origin mainly accumulate in the liver and show increased cytotoxicity. NKR, NK lineage receptors, including NK1.1, Ly49, NKG2D, CD94, and DX5.
Fig.2  Crosstalk between NKT cells and other cells in liver diseases. Several factors, including cytokines, antigen structures, and types of antigen presenting cells (APCs), can modulate NKT-cell-mediated immune responses. In the liver, NKT cell activation could lead to fibrosis, ALD, PBC, and NAFLD via activating HSC, B cells, CD8+ T cells, and NK cells, as well as killing hepatocytes through the Fas-FasL pathway. Furthermore, NKT cells are involved in the clearance of HBV, HCV, and HCC by promoting Th1 cytokine production and activation of CD8+ T cells and NK cells. Additionally, NKT cells can inhibit NAFLD by promoting Th2 cytokines, possibly through interactions with M2 macrophages, adipocytes, and hepatocytes. OPN, osteopontin; ALD, alcoholic liver disease; NAFLD, nonalcoholic fatty liver disease; PBC, primary biliary cholangitis; HCC, hepatocellular carcinoma; HSC, hepatic stellate cell; NK, natural killer cells; NKT, natural killer T cells; M2, M2 macrophage.
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