Role of liver-resident NK cells in liver immunity

The tolerogenic immune microenvironment of the liver (the immune system avoids attacking harmless antigens, such as antigens derived from food and gut microbiota) has garnered significant attention in recent years. Inherent immune cells in the liver play a unique role in regulating this microenvironment. Liver-resident natural killer (LrNK) cells, also known as liver type 1 innate lymphoid cells (ILC1s), are a recently discovered subset of immune cells that possess properties distinct from those of conventional NK (cNK) cells. Accumulating evidence suggests that there are significant differences between LrNK and cNK cells, with LrNK cells potentially exhibiting immunosuppressive functions in the liver. This review summarizes the latest findings on LrNK cells, focusing on their phenotype, heterogeneity, plasticity, origin, development, and the required transcription factors. In addition, immune functions of LrNK cells in various liver diseases, including liver cancer, viral infections, liver injury, and cirrhosis, were analyzed. By elucidating the role of LrNK cells in liver immunity, this review aims to enhance our understanding of the mechanisms underlying liver immunity and contribute to the improvement of liver disease treatment.