New insights into iNKT cells and their roles in liver diseases

Abstract

Natural killer T cells (NKTs) are an important part of the immune system. Since their discovery in the 1990s, researchers have gained deeper insights into the physiology and functions of these cells in many liver diseases. NKT cells are divided into two subsets, type I and type II. Type I NKT cells are also named iNKT cells as they express a semi-invariant T cell-receptor (TCR) α chain. As part of the innate immune system, hepatic iNKT cells interact with hepatocytes, macrophages (Kupffer cells), T cells, and dendritic cells through direct cell-to-cell contact and cytokine secretion, bridging the innate and adaptive immune systems. A better understanding of hepatic iNKT cells is necessary for finding new methods of treating liver disease including autoimmune liver diseases, alcoholic liver diseases (ALDs), non-alcoholic fatty liver diseases (NAFLDs), and liver tumors. Here we summarize how iNKT cells are activated, how they interact with other cells, and how they function in the presence of liver disease.

Inflammatory processes involved in NASH-related hepatocellular carcinoma

“…Natural Killer T (NKT) cells represent a particular subset of T-lymphocytes at the interface between innate and adaptive immunity. NKT cells are characterized by the co-expression of T-cell receptor (TCR) and the NK cell surface receptors (NK1.1 in mice or CD161/CD56 humans) [ 75 ]. The majority of hepatic NKT cells consists of type I or invariant NKT (iNKT), that use an invariant TCR encoded by Vα gene, while the remaining 5% is represented type II NKT cells relying instead on oligoclonal TCR repertoire [ 75 ].…”

“…NKT cells are characterized by the co-expression of T-cell receptor (TCR) and the NK cell surface receptors (NK1.1 in mice or CD161/CD56 humans) [ 75 ]. The majority of hepatic NKT cells consists of type I or invariant NKT (iNKT), that use an invariant TCR encoded by Vα gene, while the remaining 5% is represented type II NKT cells relying instead on oligoclonal TCR repertoire [ 75 ]. NKT cells recognize lipid antigens presented by the MHC class I-like protein CD1d and are considered key players in mediating immune responses and tumor surveillance [ 75 ].…”

“…The majority of hepatic NKT cells consists of type I or invariant NKT (iNKT), that use an invariant TCR encoded by Vα gene, while the remaining 5% is represented type II NKT cells relying instead on oligoclonal TCR repertoire [ 75 ]. NKT cells recognize lipid antigens presented by the MHC class I-like protein CD1d and are considered key players in mediating immune responses and tumor surveillance [ 75 ]. Available evidence indicates that NKT cells expand in NASH livers and plays a critical in the disease pathogenesis [ 75–77 ].…”

“…NKT cells recognize lipid antigens presented by the MHC class I-like protein CD1d and are considered key players in mediating immune responses and tumor surveillance [ 75 ]. Available evidence indicates that NKT cells expand in NASH livers and plays a critical in the disease pathogenesis [ 75–77 ]. Indeed, interfering with NKT cells effectively improves parenchymal injury, inflammation, and fibrosis in different experimental models of NASH [ 76 , 78 ].…”

Studying T Cell Responses to Hepatotropic Viruses in the Liver Microenvironment

“…Among UTC subsets, MAIT cells have been most extensively characterized in the context of chronic viral hepatitis, while data on NKT cells and γδ T cells are limited and partially contradictory [ 68 , 174 ].…”