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。
相似文献
1
Mg2+ regulates cytotoxic functions of NK and CD8 T cells in chronic EBV infection through NKG2D.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。
Science. 2013 Jul 12;341(6142):186-91. doi: 10.1126/science.1240094.
2
Magnesium and lymphoma: opportunities in translation.镁与淋巴瘤：转化医学中的机遇
Leukemia. 2014 Apr;28(4):729-31. doi: 10.1038/leu.2013.327.
3
An Update on XMEN Disease.关于 XMEN 疾病的最新进展。
J Clin Immunol. 2020 Jul;40(5):671-681. doi: 10.1007/s10875-020-00790-x. Epub 2020 May 26.
4
MAGT1-mediated disturbance of Mg homeostasis lead to exhausted of HBV-infected NK and CD8 T cells.MAGT1 介导的镁稳态紊乱导致 HBV 感染的 NK 和 CD8 T 细胞耗竭。
Sci Rep. 2017 Oct 19;7(1):13594. doi: 10.1038/s41598-017-11522-4.
5
MAGT1 messenger RNA-corrected autologous T and natural killer cells for potential cell therapy in X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection and neoplasia disease.MAGT1 信使 RNA 校正的自体 T 和自然杀伤细胞用于治疗 X 连锁免疫缺陷伴镁缺陷、EB 病毒感染和肿瘤疾病的潜在细胞疗法。
Cytotherapy. 2021 Mar;23(3):203-210. doi: 10.1016/j.jcyt.2020.08.013. Epub 2020 Oct 10.
6
X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia disease: a combined immune deficiency with magnesium defect.伴有镁缺乏、爱泼斯坦-巴尔病毒感染和肿瘤形成的X连锁免疫缺陷病：一种伴有镁缺乏的联合免疫缺陷病。
Curr Opin Pediatr. 2014 Dec;26(6):713-9. doi: 10.1097/MOP.0000000000000156.
7
Magnesium transporter 1 (MAGT1) deficiency causes selective defects in linked glycosylation and expression of immune-response genes.镁转运蛋白 1（MAGT1）缺乏导致连接糖基化和免疫反应基因表达的选择性缺陷。
J Biol Chem. 2019 Sep 13;294(37):13638-13656. doi: 10.1074/jbc.RA119.008903. Epub 2019 Jul 23.
8
A Double-Blind, Placebo-Controlled, Crossover Study of Magnesium Supplementation in Patients with XMEN Disease.一种针对 XMEN 疾病患者的镁补充剂的双盲、安慰剂对照、交叉研究。
J Clin Immunol. 2022 Jan;42(1):108-118. doi: 10.1007/s10875-021-01137-w. Epub 2021 Oct 16.
9
Lack of NKG2D in MAGT1-deficient patients is caused by hypoglycosylation.MAGT1 缺陷患者中缺乏 NKG2D 是由低聚糖基化引起的。
Hum Genet. 2022 Jul;141(7):1279-1286. doi: 10.1007/s00439-021-02400-1. Epub 2022 Feb 19.
10
Diversity of XMEN Disease: Description of 2 Novel Variants and Analysis of the Lymphocyte Phenotype.XMEN 疾病的多样性：2 种新型变异的描述及淋巴细胞表型分析。
J Clin Immunol. 2020 Feb;40(2):299-309. doi: 10.1007/s10875-019-00732-2. Epub 2019 Dec 21.
引用本文的文献
1
Biomineralized engineered -based in situ vaccination enhances antitumor immunity via sequential activation of chemo-immunotherapy.基于生物矿化工程的原位疫苗接种通过化学免疫疗法的顺序激活增强抗肿瘤免疫力。
J Immunother Cancer. 2025 Aug 17;13(8):e011799. doi: 10.1136/jitc-2025-011799.
2
Metal-based nanomedicines for cancer theranostics.用于癌症诊疗的金属基纳米药物。
Mil Med Res. 2025 Jul 30;12(1):41. doi: 10.1186/s40779-025-00627-x.
3
XMEN Disease Associated with Recurrent Autoimmune Cytopenia and EBV-Positive Hodgkin Lymphoma: A Case Report.与复发性自身免疫性血细胞减少症和EB病毒阳性霍奇金淋巴瘤相关的XMEN病：一例报告
Turk J Haematol. 2025 Aug 29;42(3):243-245. doi: 10.4274/tjh.galenos.2025.2025.0147. Epub 2025 Jul 18.
4
A genome-wide association study identifies an African-specific locus on chromosome 21q22.12 associated with Burkitt lymphoma risk and survival.一项全基因组关联研究确定了位于21号染色体22.12区域的一个非洲特异性基因座，该基因座与伯基特淋巴瘤的风险和生存相关。
Leukemia. 2025 Jul 11. doi: 10.1038/s41375-025-02690-8.
5
T cell-mediated immune surveillance conferred by latent Epstein-Barr virus genes suppresses a broad spectrum of tumor formation through NKG2D-NKG2DL interactions.潜伏的爱泼斯坦-巴尔病毒基因赋予的T细胞介导的免疫监视通过NKG2D-NKG2DL相互作用抑制广泛的肿瘤形成。
Front Immunol. 2025 Jun 4;16:1597731. doi: 10.3389/fimmu.2025.1597731. eCollection 2025.
6
Associations between ionomic profile and metabolic abnormalities in a murine model of sodium sulfide induced alopecia areata.硫化钠诱导的斑秃小鼠模型中离子组学特征与代谢异常之间的关联
Front Pharmacol. 2025 May 14;16:1507348. doi: 10.3389/fphar.2025.1507348. eCollection 2025.
7
The Importance of Vitamin D and Magnesium in Athletes.维生素D和镁对运动员的重要性。
Nutrients. 2025 May 13;17(10):1655. doi: 10.3390/nu17101655.
8
Lower Serum Magnesium Is Associated with Mortality in Severe COVID-19: A Secondary Analysis of a Randomized Trial.血清镁水平降低与重症 COVID-19 患者的死亡率相关：一项随机试验的二次分析
Biol Trace Elem Res. 2025 Apr 15. doi: 10.1007/s12011-025-04619-9.
9
Effects of two different variants in the gene on B cell subsets, platelet function, and cell glycome composition.该基因中两种不同变体对B细胞亚群、血小板功能和细胞糖组组成的影响。
Front Immunol. 2025 Mar 18;16:1547808. doi: 10.3389/fimmu.2025.1547808. eCollection 2025.
10
Magnesium and Migraine.镁与偏头痛
Nutrients. 2025 Feb 18;17(4):725. doi: 10.3390/nu17040725.
本文引用的文献
1
Rescue of impaired NK cell activity in hodgkin lymphoma with bispecific antibodies in vitro and in patients.体外和患者中双特异性抗体拯救霍奇金淋巴瘤中受损 NK 细胞活性。
Mol Ther. 2013 Apr;21(4):895-903. doi: 10.1038/mt.2013.14. Epub 2013 Mar 5.
2
NKG2D and DNAM-1 activating receptors and their ligands in NK-T cell interactions: role in the NK cell-mediated negative regulation of T cell responses.NKG2D 和 DNAM-1 激活受体及其配体在 NK-T 细胞相互作用中的作用：在 NK 细胞介导的 T 细胞反应负调控中的作用。
Front Immunol. 2013 Jan 9;3:408. doi: 10.3389/fimmu.2012.00408. eCollection 2012.
3
Structural basis of mouse cytomegalovirus m152/gp40 interaction with RAE1γ reveals a paradigm for MHC/MHC interaction in immune evasion.小鼠巨细胞病毒 m152/gp40 与 RAE1γ 相互作用的结构基础揭示了免疫逃逸中 MHC/MHC 相互作用的范例。
Proc Natl Acad Sci U S A. 2012 Dec 18;109(51):E3578-87. doi: 10.1073/pnas.1214088109. Epub 2012 Nov 19.
4
Manipulation of NKG2D ligands by cytomegaloviruses: impact on innate and adaptive immune response.巨细胞病毒对 NKG2D 配体的操纵：对先天和适应性免疫反应的影响。
Front Immunol. 2011 Dec 28;2:85. doi: 10.3389/fimmu.2011.00085. eCollection 2011.
5
Immune surveillance and therapy of lymphomas driven by Epstein-Barr virus protein LMP1 in a mouse model.在小鼠模型中，由 Epstein-Barr 病毒蛋白 LMP1 驱动的淋巴瘤的免疫监视和治疗。
Cell. 2012 Feb 17;148(4):739-51. doi: 10.1016/j.cell.2011.12.031.
6
A critical role for STAT3 transcription factor signaling in the development and maintenance of human T cell memory.STAT3 转录因子信号在人类 T 细胞记忆的发育和维持中起着关键作用。
Immunity. 2011 Nov 23;35(5):806-18. doi: 10.1016/j.immuni.2011.09.016.
7
Molecular pathogenesis of EBV susceptibility in XLP as revealed by analysis of female carriers with heterozygous expression of SAP.SAP 杂合表达女性携带者中揭示的 XLP 中 EBV 易感性的分子发病机制。
PLoS Biol. 2011 Nov;9(11):e1001187. doi: 10.1371/journal.pbio.1001187. Epub 2011 Nov 1.
8
Loss of MAGT1 abrogates the Mg2+ flux required for T cell signaling and leads to a novel human primary immunodeficiency.MAGT1 的缺失会破坏 T 细胞信号传导所需的 Mg2+ 流，从而导致一种新型的人类原发性免疫缺陷。
Magnes Res. 2011 Sep;24(3):S109-14. doi: 10.1684/mrh.2011.0286.
9
The cytotoxic potential of interleukin-15-stimulated cytokine-induced killer cells against leukemia cells.白细胞介素-15 刺激的细胞因子诱导的杀伤细胞对白血病细胞的细胞毒性潜力。
Cytotherapy. 2012 Jan;14(1):91-103. doi: 10.3109/14653249.2011.613931. Epub 2011 Oct 6.
10
Dual-functional capability of CD3+CD56+ CIK cells, a T-cell subset that acquires NK function and retains TCR-mediated specific cytotoxicity.CD3+CD56+ CIK 细胞兼具双重功能，是一种获得 NK 功能并保留 TCR 介导的特异性细胞毒性的 T 细胞亚群。
Blood. 2011 Sep 22;118(12):3301-10. doi: 10.1182/blood-2011-02-336321. Epub 2011 Aug 5.
Zotero 插件