The Effect Of Liver Microenvironment On Development Of Hepatic NK And NKT Cells

The precursors of NK cells and NKT cells are derived from the bone marrow;they are committed to the NK cell and NKT cell lineage and develop into mature NK cells with full effector function and heterogeneous phenotypes.NK cell precursors are found in different organs, such as bone marrow, fetal thymus, lymph node (LN), liver, spleen and peripheral blood, whereas immature NK (iNK) cells are found in the bone marrow, liver and spleen. It is unknown whether these developmental intermediates leave the bone marrow to complete their differentiation elsewhere, such as the liver and spleen.Immature NKT cells of thymus do not express NK1.1.They undergo mature process in periphery and then express NK1.1.As an lymphoid organ, liver is an important site for NKT cells maturing in periphery. Stromal cells in various organs send signals through cytokines that influence the ultimate phenotypes and functions of NK cell precursors.In our study, the development of NK cells in liver was explored and compared with NK cell development in spleen during mouse ontogeny by Flow cytometry.We also explored the impact of IFN-gamma on the distribution and function of hepatic NK cells.The CD27-CD11b-NK cell precursors accumulated predominantly in the adult liver and not in the spleen. In the liver, more immature NK cells were present, which express a higher level of NKG2A and lower levels of Ly49receptors. Additionally, different stimulatory receptors and adhesion molecules were expressed on NK cells in the liver and spleen during ontogeny. These results indicate that there might be a specific developmental pathway of NK cells in the liver and that the microenvironments play important roles in NK cell development and differentiation. Futhermore, we exhibited that the percentages and numbers of mature NK cells were declined significantly in the liver from adult IFN-gamma deficient mouse GKO mouse uniquely. Moreover, the NK cell subsets and phenotypes were specifically in the liver of IFN-gamma deficient mouse. However, Lin-CD122+NK progenitor cells develop normally in the liver and bone marrow of adult IFN-gamma deficient mouse. Furthermore, deficiency of IFN-gamma resulted to weak expressed of CD69and functional molecular by hepatic NK cells. All these data demonstrated that IFN-gamma may play important role to sustain the unique environment of liver and affect the development of hepatic NK cells.Futhermore, we found that there were a subset immature NKT cells in the liver, and we explored the developmental stages and subsets of hepatic NKT cells during mouse ontogeny.