Institute of Immunology, Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
Cytokine. 2012 Dec;60(3):616-25. doi: 10.1016/j.cyto.2012.07.012. Epub 2012 Aug 24.
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.
已有研究明确表明，IFN-γ 在 T 细胞、B 细胞和巨噬细胞的分化和成熟中发挥重要作用；然而，目前尚不清楚 NK 细胞的发育是否受 IFN-γ 调控。在本研究中，我们利用 IFN-γ 缺陷型（GKO）小鼠发现，成年 IFN-γ（-/-）小鼠肝脏中 NK1.1（+）CD3（-）细胞的比例和数量显著下降，但在脾脏、骨髓和淋巴结中未见明显变化。然而，IFN-γ（-/-）小鼠的肝脏和骨髓中 Lin（-）CD122（+）NK 祖细胞均正常发育。此外，IFN-γ（-/-）小鼠肝脏中更成熟的 CD27（-）CD11b（+）NK 细胞积累增加。IFN-γ 缺陷导致肝脏 NK1.1（+）CD3（-）细胞 CD69、GranzymeB 和 TRAIL 的表达降低，IFN-γ（-/-）肝脏 NK1.1（+）CD3（-）细胞的表型与 WT 肝脏 NK 细胞不同。体内用 Poly（I:C）刺激后，IFN-γ（-/-）小鼠肝脏中 NK1.1（+）CD3（-）细胞积累减少，GranzymeB、TRAIL 和 FasL 的表达减弱。综上，这些结果表明 IFN-γ 对 NK 细胞在肝脏中的发育具有重要作用。
