The liver works as a school to educate regulatory immune cells

Abstract

Because of its unique blood supply, the liver maintains a special local immune tolerogenic microenvironment. Moreover, the liver can impart this immune tolerogenic effect on other organs, thus inducing systemic immune tolerance. The network of hepatic regulatory cells is an important mechanism underlying liver tolerance. Many types of liver-resident antigen-presenting cells (APCs) have immune regulatory function, and more importantly, they can also induce the differentiation of circulating immune cells into regulatory cells to further extend systemic tolerance. Thus, the liver can be seen as a type of 'school', where liver APCs function as 'teachers' and circulating immune cells function as 'students.'

Figure 1

Crosstalk between the liver and other organs can regulate immunity in other organs. Unlike other immune-privileged organs, the liver contains many types of immune cells. (1) The immune response often occurs in the liver during virus infection, transplantation, ectopic antigen expression and so on. (2) The liver can sometimes generate a positive immune response to eliminate various ‘enemies', (3) which is followed by the generation of immune defense throughout the body. (4) Immune tolerance is more often induced, allowing foreign antigens to persist in the liver. (5) Additionally, the liver can crosstalk with other organs and regulate their immune responses, effectively inducing systemic tolerance. (6) After transferring immune tolerance from the liver to the entire body, systemic immune responses are suppressed, allowing for virus infection, tumor migration, transplant acceptance and so on. CNS, central nervous system; LN, lymph node.

Figure 2

The regulatory network among the ‘teachers' and ‘students' in the liver. The resident hepatic cells (teachers), including hepatocytes, Kupffer cells, DCs, LSECs and HSCs, form a loose blood supply channel called the sinusoid. This unique structure gives the resident cells sufficient room and time to encounter and regulate circulating cells (students), including T cells, NK cells, NKT cells and MDSCs. The crosstalk between the teachers and students forms a complex regulatory network. The effect of the education process on each pair of interacting cells is summarized in Table 1. DC, dendritic cell; HSC, hepatic stellate cell; LSEC, liver sinusoidal endothelial cell; MDSC, myeloid-derived suppressor cell; NK, natural killer cell; NKT, natural killer T cell.