镁离子通过 NKG2D 调节慢性 EBV 感染中 NK 和 CD8 T 细胞的细胞毒性功能。
Mg2+ regulates cytotoxic functions of NK and CD8 T cells in chronic EBV infection through NKG2D.
机构信息
Molecular Development of the Immune System Section, Lymphocyte Molecular Genetics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
出版信息
Science. 2013 Jul 12;341(6142):186-91. doi: 10.1126/science.1240094.
Abstract
The magnesium transporter 1 (MAGT1) is a critical regulator of basal intracellular free magnesium (Mg(2+)) concentrations. Individuals with genetic deficiencies in MAGT1 have high levels of Epstein-Barr virus (EBV) and a predisposition to lymphoma. We show that decreased intracellular free Mg(2+) causes defective expression of the natural killer activating receptor NKG2D in natural killer (NK) and CD8(+) T cells and impairs cytolytic responses against EBV. Notably, magnesium supplementation in MAGT1-deficient patients restores intracellular free Mg(2+) and NKG2D while concurrently reducing EBV-infected cells in vivo, demonstrating a link between NKG2D cytolytic activity and EBV antiviral immunity in humans. Moreover, these findings reveal a specific molecular function of free basal intracellular Mg(2+) in eukaryotic cells.
摘要
镁转运蛋白 1（MAGT1）是调节基础细胞内游离镁（Mg(2+)）浓度的关键调控因子。MAGT1 基因缺陷的个体，其 EBV（Epstein-Barr virus）水平较高，且易患淋巴瘤。我们发现，细胞内游离镁（Mg(2+)）减少会导致自然杀伤（NK）和 CD8(+)T 细胞中自然杀伤激活受体 NKG2D 的表达缺陷，并损害针对 EBV 的细胞溶解反应。值得注意的是，MAGT1 缺陷患者的镁补充可恢复细胞内游离镁（Mg(2+)）和 NKG2D，同时减少体内 EBV 感染细胞，这表明人类的 NKG2D 细胞溶解活性与 EBV 抗病毒免疫之间存在联系。此外，这些发现揭示了游离基础细胞内镁（Mg(2+)）在真核细胞中的特定分子功能。
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