• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

细胞增殖减少通过限制 FcεRIγ 表达促进自然杀伤细胞适应性样表型。

Diminished cell proliferation promotes natural killer cell adaptive-like phenotype by limiting FcεRIγ expression.

机构信息

Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA.

Parker Institute for Cancer Immunotherapy, University of California, San Francisco, San Francisco, CA.

出版信息

J Exp Med. 2022 Nov 7;219(11). doi: 10.1084/jem.20220551. Epub 2022 Sep 6.

DOI:10.1084/jem.20220551
PMID:36066491
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9448639/
Abstract

Human adaptive-like natural killer (NK) cells express low levels of FcεRIγ (FcRγ-/low) and are reported to accumulate during COVID-19 infection; however, the mechanism underlying and regulating FcRγ expression in NK cells has yet to be fully defined. We observed lower FcRγ protein expression in NK cell subsets from lung transplant patients during rapamycin treatment, suggesting a link with reduced mTOR activity. Further, FcRγ-/low NK cell subsets from healthy donors displayed reduced mTOR activity. We discovered that FcRγ upregulation is dependent on cell proliferation progression mediated by IL-2, IL-15, or IL-12, is sensitive to mTOR suppression, and is inhibited by TGFβ or IFNα. Accordingly, the accumulation of adaptive-like FcRγ-/low NK cells in COVID-19 patients corresponded to increased TGFβ and IFNα levels and disease severity. Our results show that an adaptive-like NK cell phenotype is induced by diminished cell proliferation and has an early prognostic value for increased TGFβ and IFNα levels in COVID-19 infection associated with disease severity.

摘要

人类适应性样自然杀伤 (NK) 细胞表达低水平的 FcεRIγ（FcRγ-/low），据报道在 COVID-19 感染期间会积累；然而，NK 细胞中 FcRγ 表达的调节机制尚未完全定义。我们观察到肺移植患者在雷帕霉素治疗期间 NK 细胞亚群中 FcRγ 蛋白表达降低，这表明与 mTOR 活性降低有关。此外，来自健康供体的 FcRγ-/low NK 细胞亚群显示出降低的 mTOR 活性。我们发现 FcRγ 的上调依赖于由 IL-2、IL-15 或 IL-12 介导的细胞增殖进展，对 mTOR 抑制敏感，并受 TGFβ 或 IFNα 抑制。因此，COVID-19 患者中适应性样 FcRγ-/low NK 细胞的积累与 TGFβ 和 IFNα 水平升高以及疾病严重程度相关。我们的研究结果表明，一种适应性样 NK 细胞表型是由细胞增殖减少诱导的，并且对 COVID-19 感染中与疾病严重程度相关的 TGFβ 和 IFNα 水平升高具有早期预后价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/248e/9448639/0f43921c2e95/JEM_20220551_FigS5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/248e/9448639/e57384068d00/JEM_20220551_GA.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/248e/9448639/7138eeed836b/JEM_20220551_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/248e/9448639/da37d82aa631/JEM_20220551_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/248e/9448639/11e994e3c4e8/JEM_20220551_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/248e/9448639/63e99701115d/JEM_20220551_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/248e/9448639/7447d9ffb4d6/JEM_20220551_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/248e/9448639/2a83b7e93e77/JEM_20220551_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/248e/9448639/6a1582270751/JEM_20220551_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/248e/9448639/0063c68a15a0/JEM_20220551_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/248e/9448639/be13eae49a25/JEM_20220551_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/248e/9448639/a203d1ff748a/JEM_20220551_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/248e/9448639/a5574ed217c0/JEM_20220551_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/248e/9448639/0f43921c2e95/JEM_20220551_FigS5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/248e/9448639/e57384068d00/JEM_20220551_GA.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/248e/9448639/7138eeed836b/JEM_20220551_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/248e/9448639/da37d82aa631/JEM_20220551_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/248e/9448639/11e994e3c4e8/JEM_20220551_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/248e/9448639/63e99701115d/JEM_20220551_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/248e/9448639/7447d9ffb4d6/JEM_20220551_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/248e/9448639/2a83b7e93e77/JEM_20220551_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/248e/9448639/6a1582270751/JEM_20220551_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/248e/9448639/0063c68a15a0/JEM_20220551_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/248e/9448639/be13eae49a25/JEM_20220551_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/248e/9448639/a203d1ff748a/JEM_20220551_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/248e/9448639/a5574ed217c0/JEM_20220551_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/248e/9448639/0f43921c2e95/JEM_20220551_FigS5.jpg

相似文献

1
Diminished cell proliferation promotes natural killer cell adaptive-like phenotype by limiting FcεRIγ expression.细胞增殖减少通过限制 FcεRIγ 表达促进自然杀伤细胞适应性样表型。
J Exp Med. 2022 Nov 7;219(11). doi: 10.1084/jem.20220551. Epub 2022 Sep 6.
2
Relationship of NKG2C Copy Number with the Distribution of Distinct Cytomegalovirus-Induced Adaptive NK Cell Subsets.NKG2C基因拷贝数与不同巨细胞病毒诱导的适应性自然杀伤细胞亚群分布的关系
J Immunol. 2016 May 1;196(9):3818-27. doi: 10.4049/jimmunol.1502438. Epub 2016 Mar 18.
3
Adaptive Features of Natural Killer Cells in Multiple Sclerosis.自然杀伤细胞在多发性硬化症中的适应性特征。
Front Immunol. 2019 Oct 15;10:2403. doi: 10.3389/fimmu.2019.02403. eCollection 2019.
4
Identification of human NK cells that are deficient for signaling adaptor FcRγ and specialized for antibody-dependent immune functions.鉴定人 NK 细胞中信号转导衔接蛋白 FcRγ 缺陷的细胞，并专门研究其在抗体依赖的免疫功能中的作用。
Int Immunol. 2012 Dec;24(12):793-802. doi: 10.1093/intimm/dxs080. Epub 2012 Sep 7.
5
Dynamic Changes in Natural Killer Cell Subset Frequencies in the Absence of Cytomegalovirus Infection.自然杀伤细胞亚群频率在无巨细胞病毒感染时的动态变化。
Front Immunol. 2019 Nov 22;10:2728. doi: 10.3389/fimmu.2019.02728. eCollection 2019.
6
An Inverse Relationship Between c-Kit/CD117 and mTOR Confers NK Cell Dysregulation Late After Severe Injury.严重损伤后，c-Kit/CD117 与 mTOR 之间的负相关关系导致 NK 细胞失调。
Front Immunol. 2020 Jun 25;11:1200. doi: 10.3389/fimmu.2020.01200. eCollection 2020.
7
IL-18 Responsiveness Defines Limitations in Immune Help for Specialized FcRγ NK Cells.IL-18 反应性定义了专门 FcRγ NK 细胞免疫辅助的局限性。
J Immunol. 2020 Dec 15;205(12):3429-3442. doi: 10.4049/jimmunol.2000430. Epub 2020 Nov 13.
8
Untimely TGFβ responses in COVID-19 limit antiviral functions of NK cells.COVID-19 中 TGFβ 的过早反应限制了 NK 细胞的抗病毒功能。
Nature. 2021 Dec;600(7888):295-301. doi: 10.1038/s41586-021-04142-6. Epub 2021 Oct 25.
9
TGF-β inhibits the activation and functions of NK cells by repressing the mTOR pathway.TGF-β 通过抑制 mTOR 通路来抑制 NK 细胞的激活和功能。
Sci Signal. 2016 Feb 16;9(415):ra19. doi: 10.1126/scisignal.aad1884.
10
Natural Killer Cells Adapt to Cytomegalovirus Along a Functionally Static Phenotypic Spectrum in Human Immunodeficiency Virus Infection.自然杀伤细胞沿着功能静态表型谱适应巨细胞病毒在人类免疫缺陷病毒感染。
Front Immunol. 2018 Nov 12;9:2494. doi: 10.3389/fimmu.2018.02494. eCollection 2018.

引用本文的文献

1
CITE-Seq Analysis Reveals a Differential Natural Killer Cell Expression in Cardiovascular Disease Patients Impacted by Human-Cytomegalovirus Serostatus and Diabetes.CITE-Seq分析揭示了受人类巨细胞病毒血清状态和糖尿病影响的心血管疾病患者中自然杀伤细胞的差异表达。
Int J Mol Sci. 2025 Feb 6;26(3):1369. doi: 10.3390/ijms26031369.
2
Single-cell profiling aligns CD56 and cytomegalovirus-induced adaptive natural killer cells to a naïve-memory relationship.单细胞分析将CD56和巨细胞病毒诱导的适应性自然杀伤细胞与一种幼稚-记忆关系联系起来。
Front Immunol. 2024 Dec 17;15:1499492. doi: 10.3389/fimmu.2024.1499492. eCollection 2024.
3

本文引用的文献

1
Differential IL-12 signaling induces human natural killer cell activating receptor-mediated ligand-specific expansion.差异化的 IL-12 信号诱导人类自然杀伤细胞激活受体介导的配体特异性扩增。
J Exp Med. 2022 Aug 1;219(8). doi: 10.1084/jem.20212434. Epub 2022 Jun 27.
2
The CD3ζ adaptor structure determines functional differences between human and mouse CD16 Fc receptor signaling.CD3ζ 衔接子结构决定了人源和鼠源 CD16 Fc 受体信号转导的功能差异。
J Exp Med. 2022 May 2;219(5). doi: 10.1084/jem.20220022. Epub 2022 Mar 23.
3
Untimely TGFβ responses in COVID-19 limit antiviral functions of NK cells.
NK Cells: Not Just Followers But Also Initiators of Chronic Vascular Rejection.
自然杀伤细胞：不只是慢性血管排斥反应的追随者，也是其启动者。
Transpl Int. 2024 Oct 16;37:13318. doi: 10.3389/ti.2024.13318. eCollection 2024.
4
CD94 natural killer cells potentiate pulmonary ischaemia-reperfusion injury.CD94 自然杀伤细胞增强肺缺血再灌注损伤。
Eur Respir J. 2024 Sep 26;64(3). doi: 10.1183/13993003.02171-2023. Print 2024 Sep.
5
BCG priming followed by a novel interleukin combination activates Natural Killer cells to selectively proliferate and become anti-tumour long-lived effectors.BCG 预刺激联合新型白细胞介素组合激活自然杀伤细胞，选择性增殖并成为抗肿瘤的长效效应细胞。
Sci Rep. 2024 Jun 7;14(1):13133. doi: 10.1038/s41598-024-62968-2.
6
HLA-DR Expression in Natural Killer Cells Marks Distinct Functional States, Depending on Cell Differentiation Stage.自然杀伤细胞中 HLA-DR 的表达标志着不同的功能状态，这取决于细胞分化阶段。
Int J Mol Sci. 2024 Apr 23;25(9):4609. doi: 10.3390/ijms25094609.
7
Interleukin-2 is required for NKp30-dependent NK cell cytotoxicity by preferentially regulating NKp30 expression.白细胞介素-2通过优先调节NKp30的表达，对NKp30依赖的NK细胞细胞毒性是必需的。
Front Immunol. 2024 Apr 18;15:1388018. doi: 10.3389/fimmu.2024.1388018. eCollection 2024.
8
Powerful and accurate detection of temporal gene expression patterns from multi-sample multi-stage single-cell transcriptomics data with TDEseq.利用 TDEseq 从多样本多阶段单细胞转录组学数据中强大而准确地检测时间基因表达模式。
Genome Biol. 2024 Apr 15;25(1):96. doi: 10.1186/s13059-024-03237-3.
9
Autologous T-Cell-Free Antigen Presentation System Unveils hCMV-Specific NK Cell Response.自体 T 细胞游离抗原呈递系统揭示 hCMV 特异性 NK 细胞反应。
Cells. 2024 Mar 17;13(6):530. doi: 10.3390/cells13060530.
10
Integrative systems biology reveals NKG2A-biased immune responses correlate with protection in infectious disease, autoimmune disease, and cancer.整合系统生物学揭示，NKG2A 偏向性免疫反应与传染病、自身免疫性疾病和癌症的保护相关。
Cell Rep. 2024 Mar 26;43(3):113872. doi: 10.1016/j.celrep.2024.113872. Epub 2024 Feb 29.
COVID-19 中 TGFβ 的过早反应限制了 NK 细胞的抗病毒功能。
Nature. 2021 Dec;600(7888):295-301. doi: 10.1038/s41586-021-04142-6. Epub 2021 Oct 25.
4
Early IFN-α signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19.早期 IFN-α 特征和持续功能障碍是严重 COVID-19 中 NK 细胞的显著特征。
Immunity. 2021 Nov 9;54(11):2650-2669.e14. doi: 10.1016/j.immuni.2021.09.002. Epub 2021 Sep 4.
5
Antibody-dependent cellular cytotoxicity response to SARS-CoV-2 in COVID-19 patients.COVID-19 患者对 SARS-CoV-2 的抗体依赖细胞细胞毒性反应。
Signal Transduct Target Ther. 2021 Sep 24;6(1):346. doi: 10.1038/s41392-021-00759-1.
6
Single-cell profiling identifies impaired adaptive NK cells expanded after HCMV reactivation in haploidentical HSCT.单细胞分析鉴定出在单倍体 HSCT 中 HCMV 再激活后扩增的适应性 NK 细胞受损。
JCI Insight. 2021 Jun 22;6(12):146973. doi: 10.1172/jci.insight.146973.
7
Deconvoluting global cytokine signaling networks in natural killer cells.解析自然杀伤细胞中的全球细胞因子信号转导网络。
Nat Immunol. 2021 May;22(5):627-638. doi: 10.1038/s41590-021-00909-1. Epub 2021 Apr 15.
8
Early Adaptive Natural Killer Cell Expansion Is Associated with Decreased Relapse After Autologous Transplantation for Multiple Myeloma.早期适应性自然杀伤细胞扩增与多发性骨髓瘤自体移植后复发减少相关。
Transplant Cell Ther. 2021 Apr;27(4):310.e1-310.e6. doi: 10.1016/j.jtct.2020.10.023. Epub 2020 Dec 17.
9
Expansions of adaptive-like NK cells with a tissue-resident phenotype in human lung and blood.人类肺部和血液中具有组织驻留表型的适应性样 NK 细胞的扩增。
Proc Natl Acad Sci U S A. 2021 Mar 16;118(11). doi: 10.1073/pnas.2016580118.
10
Transcription Factors Associated With IL-15 Cytokine Signaling During NK Cell Development.与 NK 细胞发育过程中 IL-15 细胞因子信号相关的转录因子。
Front Immunol. 2021 Mar 18;12:610789. doi: 10.3389/fimmu.2021.610789. eCollection 2021.