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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) : 269-279
Natural killer cells in liver diseases
Meijuan Zheng1(), Haoyu Sun2, Zhigang Tian2,3
1. Department of Clinical Laboratory, First Affiliated Hospital of Anhui Medical University, Hefei 230022, China
2. Institute of Immunology, Key Laboratory of Innate Immunity and Chronic Disease of Chinese Academy of Sciences, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei 230027, China
3. Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China
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The liver has been characterized as a frontline lymphoid organ with complex immunological features such as liver immunity and liver tolerance. Liver tolerance plays an important role in liver diseases including acute inflammation, chronic infection, autoimmune disease, and tumors. The liver contains a large proportion of natural killer (NK) cells, which exhibit heterogeneity in phenotypic and functional characteristics. NK cell activation, well known for its role in the immune surveillance against tumor and pathogen-infected cells, depends on the balance between numerous activating and inhibitory signals. In addition to the innate direct “killer” functions, NK cell activity contributes to regulate innate and adaptive immunity (helper or regulator). Under the setting of liver diseases, NK cells are of great importance for stimulating or inhibiting immune responses, leading to either immune activation or immune tolerance. Here, we focus on the relationship between NK cell biology, such as their phenotypic features and functional diversity, and liver diseases.

Keywords natural killer cell      phenotype      immune activation      immune tolerance      liver diseases     
Corresponding Authors: Meijuan Zheng   
Just Accepted Date: 12 February 2018   Online First Date: 17 April 2018    Issue Date: 04 May 2018
 Cite this article:   
Meijuan Zheng,Haoyu Sun,Zhigang Tian. Natural killer cells in liver diseases[J]. Front. Med., 2018, 12(3): 269-279.
Fig.1  NK cell exhaustion may be the prelude of CD8+ T cell exhaustion. In chronic infection and HCC, effector NK cells become exhausted with increased expressions of inhibitory receptors, such as Tim-3, NKG2A, and PD-1; decreased expressions of activating receptors including NKG2D and NKp30; and decreased expressions of transcription factors, such as and T-bet. And exhausted NK cells may lead to CD8+ T cell exhaustion in chronic infection and tumor conditions.
Fig.2  NK cell activity in liver immunology. NK cells activate T cells through either direct or indirect regulatory mechanisms, leading to liver immunity in acute infection, inflammation, and autoimmune disease. Under chronic infection and tumor conditions, NK cells negatively regulate T cell immunity and induce anergic T cells and Treg cells via direct or indirect mechanisms, which maintain liver tolerance. And NK cell exhaustion may be involved in liver tolerance and associated with exhausted CD8+ T cells in chronic liver disease.
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