Impairment of hepatic NK cell development in IFN-γ deficient mice

Abstract

It is already clearly demonstrated that IFN-γ plays important roles in differentiation and maturation of T cells, B cells and macrophages; however, it is not clear whether NK cell development is regulated by IFN-γ. In our study by using IFN-γ-deficient mice (GKO), we observed that the percentage and number of NK1.1+CD3− cells were declined significantly in the liver, but not in the spleen, bone marrow and lymph node, of adult IFN-γ−/− mice. However, Lin−CD122+ NK progenitor cells developed normally both in liver and bone marrow in IFN-γ−/− mice. Moreover, more mature CD27−CD11b+ NK cells accumulated in the liver of IFN-γ−/− mice. Deficiency of IFN-γ resulted in the lower expression of CD69, GranzymeB and TRAIL by hepatic NK1.1+CD3− cells and the phenotypes of IFN-γ−/− hepatic NK1.1+CD3− cells were altered from WT hepatic NK cells. When stimulated with Poly (I:C) in vivo, attenuated accumulating in the liver and weaker expression of GranzymeB, TRAIL and FasL of NK1.1+CD3− cells were observed of IFN-γ−/− mice. Accordingly, these results demonstrate that IFN-γ plays important role in mounting liver environment for development of hepatic NK cells.