Zafirova Biljana, Mandarić Sanja, Antulov Ronald, Krmpotić Astrid, Jonsson Helena, Yokoyama Wayne M, Jonjić Stipan, Polić Bojan
Department of Histology and Embryology, University of Rijeka School of Medicine, B. Branchetta 20, HR-51000 Rijeka, Croatia.
Immunity. 2009 Aug 21;31(2):270-82. doi: 10.1016/j.immuni.2009.06.017. Epub 2009 Jul 23.
NKG2D is a potent activating receptor on natural killer (NK) cells and acts as a molecular sensor for stressed cells expressing NKG2D ligands such as infected or tumor-transformed cells. Although NKG2D is expressed on NK cell precursors, its role in NK cell development is not known. We have generated NKG2D-deficient mice by targeting the Klrk1 locus. Here we provide evidence for an important regulatory role of NKG2D in the development of NK cells. The absence of NKG2D caused faster division of NK cells, perturbation in size of some NK cell subpopulations, and their augmented sensitivity to apoptosis. As expected, Klrk1(-/-) NK cells are less responsive to tumor targets expressing NKG2D ligands. Klrk1(-/-) mice, however, showed an enhanced NK cell-mediated resistance to mouse cytomegalovirus infection as a consequence of NK cell dysregulation. Altogether, these findings provide evidence for regulatory function of NKG2D in NK cell physiology.
NKG2D是自然杀伤（NK）细胞上一种强大的激活受体，可作为表达NKG2D配体的应激细胞（如受感染或肿瘤转化细胞）的分子传感器。尽管NKG2D在NK细胞前体上表达，但其在NK细胞发育中的作用尚不清楚。我们通过靶向Klrk1基因座生成了NKG2D缺陷小鼠。在此，我们提供了NKG2D在NK细胞发育中具有重要调节作用的证据。NKG2D的缺失导致NK细胞分裂加快，一些NK细胞亚群的大小受到扰动，并且它们对细胞凋亡的敏感性增强。正如预期的那样，Klrk1（-/-）NK细胞对表达NKG2D配体的肿瘤靶标反应较弱。然而，由于NK细胞失调，Klrk1（-/-）小鼠对小鼠巨细胞病毒感染表现出增强的NK细胞介导的抵抗力。总之，这些发现为NKG2D在NK细胞生理学中的调节功能提供了证据。
