**4.6 NK, ILC cells and NKT cells**

Natural killer cells represent 30–50% of hepatic lymphocytes [63]. They differ from conventional NK cells and are closer to innate lymphoid cells (ILCs). In mouse they are closer to ILCs1, because of the expression of NK1.1 (CD161), CD69, CD49a NKp46, TRAIL. Both in mouse and human, these cells express CD49a and CD69 and secrete IFN-g and TNFa, but have weak suppressive capacity [64]. The third subset NKT cells are well presented in the liver. Different subsets are differentially presented in mice and humans, but have similar function – support immune homeostasis, control autoimmune reactions and immune responses to microbial and viral infections and cancer [65]. Of particular interest are invariant NKT and mucosal-associated invariant T cells (MAIT). They are CD3<sup>+</sup> CD4<sup>−</sup> CD161<sup>+</sup> Vα7.2<sup>+</sup> cells and have robust IFN-g and granzymes B response to inflammatory signal, but limited responsiveness when stimulated directly via TCR [66, 67].

Therefore, the proper hepatic cells have dual function. On one hand they are involved in metabolic processes in the liver and on the other – they participate in immune-mediated reactions per se and by carrying out the function of a bridge between biochemical reactions and immune pathways.

Hepatic cells interact with local immune cells and thus actively participate in the establishment of a sustained immune tolerant milieu. Zheng and Tian (2019) analyzing current data, highlight the death of effector cells and the "education" of regulatory cells as key processes leading to the development of liver tolerance. Additionally, they describe a broad spectrum of baseline immune mechanisms responsible for the state of hyporesponsiveness – clonal deletion, clonal anergy, clonal deviation, T cell dysfunction/exhaustion, education etc. [68].
