Sharma Neekun, Trinidad Camille V, Trembath Andrew P, Markiewicz Mary A
Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, KS 66160.
Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, KS 66160
J Immunol. 2017 Oct 15;199(8):2865-2872. doi: 10.4049/jimmunol.1700647. Epub 2017 Sep 11.
NK group 2 member D (NKG2D) is a strong NK cell-activating receptor, with engagement by ligands triggering granule release and cytokine production. The function of NKG2D signaling in NK cells has largely been studied in the context of engagement of the receptor by ligands expressed on the surface of target cells. We report that upon activation with IL-12, IL-15, and IL-18 human NK cells express NKG2D ligands of the UL16 binding protein family on the cell surface. NKG2D-ligand interaction between cytokine-stimulated NK cells increases the activity of the metalloprotease TNF-α-converting enzyme. This enhanced TNF-α-converting enzyme activity significantly increases the release of TNF-α and UL16 binding protein from the surface of the NK cells. These results demonstrate that NKG2D signaling is critical for maximal TNF-α release by NK cells. Further, they demonstrate a role for NKG2D-ligand interaction via homotypic NK cell contact in NK cell effector function.
自然杀伤细胞2族成员D（NKG2D）是一种强大的自然杀伤细胞激活受体，其与配体结合可触发颗粒释放和细胞因子产生。自然杀伤细胞中NKG2D信号传导的功能主要是在受体与靶细胞表面表达的配体结合的背景下进行研究的。我们报告，在用白细胞介素-12、白细胞介素-15和白细胞介素-18激活后，人自然杀伤细胞在细胞表面表达UL16结合蛋白家族的NKG2D配体。细胞因子刺激的自然杀伤细胞之间的NKG2D-配体相互作用增加了金属蛋白酶肿瘤坏死因子-α转化酶的活性。这种增强后的肿瘤坏死因子-α转化酶活性显著增加了肿瘤坏死因子-α和UL16结合蛋白从自然杀伤细胞表面的释放。这些结果表明，NKG2D信号传导对于自然杀伤细胞最大程度释放肿瘤坏死因子-α至关重要。此外，它们证明了通过同型自然杀伤细胞接触的NKG2D-配体相互作用在自然杀伤细胞效应功能中的作用。
