Cure Alveolar Soft Part Sarcoma International (iCureASPS)

Abstract

The liver represents a frontline immune organ that is constantly exposed to a variety of gut-derived antigens as a result of its unique location and blood supply. With a predominant role in innate immunity, the liver is enriched with various innate immune cells, among which natural killer (NK) cells play important roles in host defense and in maintaining immune balance. Hepatic NK cells were first described as ‘pit cells' in the rat liver in the 1970s. Recent studies of NK cells in mouse and human livers have shown that two distinct NK cell subsets, liver-resident NK cells and conventional NK (cNK) cells, are present in this organ. Here, we review liver NK cell subsets in different species, revisiting rat hepatic pit cells and highlighting recent progress related to resident NK cells in mouse and human livers, and also discuss the dual roles of NK cells in liver immunity.

Keywords: conventional NK cell, liver, liver-resident NK cell, pit cell, tolerance


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4856807/

Abstract

Natural killer (NK) cells are enriched in lymphocytes within the liver and have unique phenotypic features and functional properties, including TRAIL-dependent cytotoxicity and specific cytokine profiles. As a key component of innate immunity in the liver, NK cells perform critical roles in host defense against pathogens and tumors via their natural cytotoxicity and cytokine production, and they also act as regulatory cells by engaging in reciprocal interactions with other types of liver cells through cell-to-cell contact and the production of cytokines. Accumulating evidence from the last decade suggests that NK cells play an important role in controlling viral hepatitis, liver fibrosis, and liver tumorigenesis but also contribute to the pathogenesis of liver injury and inflammation. The characterization of intrahepatic NK cell functions has not only helped us to better understand the pathogenesis of liver disease but has also revealed new therapeutic targets for managing this disease.

Keywords: viral hepatitis, liver fibrosis, liver tumor, cytokine, NKG2D
Natural killer (NK) cells were functionally identified in 1975 as a unique subset of lymphocytes based on the presence of distinctive cytoplasmic granules. Currently, the understanding of NK cell biology and function is much clearer. Consistent with their roles in immune defense and surveillance, NK cells are widely distributed in the body throughout lymphoid and non-lymphoid tissues. The tissue with the highest frequency of NK cells among its lymphocytes is the lung, followed by the liver, the peripheral blood, the spleen, the bone marrow, the lymph nodes, and the thymus. Accumulating evidence suggests that NK cell functions are strongly influenced by the tissue microenvironment. In particular, NK cells within a healthy liver exhibit a higher level of cytotoxicity against tumor cells and express higher levels of cytotoxicity mediators when compared with peripheral NK cells. 1, 2 Healthy liver NK cells can be further activated during chronic hepatitis (HCV) virus infection or by IFN-α antiviral therapy,3-5 playing critical roles in controlling viral hepatitis3-5 and liver fibrogenesis,5-10 although a recent study suggests that intrahepatic NK cell cytotoxic function is impaired in chronic HCV infection.11 In addition, chronic alcohol consumption is associated with the suppression of liver NK cell functions, which contributes to the pathogenesis of alcoholic liver disease.12 In this review, we highlight recent advances in the understanding of NK cell functions in the anti-viral, anti-fibrotic, and anti-tumor responses in the liver and briefly discuss the potential of NK cells as therapeutic targets for the treatment of liver disease.

https://www.ncbi.nlm.nih.gov/pmc/articl ... 7/#S1title