• 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

人类免疫衰老的染色质可及性特征源于CD8 T细胞。

The chromatin accessibility signature of human immune aging stems from CD8 T cells.

作者信息

Ucar Duygu, Márquez Eladio J, Chung Cheng-Han, Marches Radu, Rossi Robert J, Uyar Asli, Wu Te-Chia, George Joshy, Stitzel Michael L, Palucka A Karolina, Kuchel George A, Banchereau Jacques

机构信息

The Jackson Laboratory for Genomic Medicine, Farmington, CT

Institute for Systems Genomics, University of Connecticut, Farmington, CT.

出版信息

J Exp Med. 2017 Oct 2;214(10):3123-3144. doi: 10.1084/jem.20170416. Epub 2017 Sep 13.

DOI:10.1084/jem.20170416
PMID:28904110
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5626401/
Abstract

Aging is linked to deficiencies in immune responses and increased systemic inflammation. To unravel the regulatory programs behind these changes, we applied systems immunology approaches and profiled chromatin accessibility and the transcriptome in PBMCs and purified monocytes, B cells, and T cells. Analysis of samples from 77 young and elderly donors revealed a novel and robust aging signature in PBMCs, with simultaneous systematic chromatin closing at promoters and enhancers associated with T cell signaling and a potentially stochastic chromatin opening mostly found at quiescent and repressed sites. Combined analyses of chromatin accessibility and the transcriptome uncovered immune molecules activated/inactivated with aging and identified the silencing of the gene and the IL-7 signaling pathway genes as potential biomarkers. This signature is borne by memory CD8 T cells, which exhibited an aging-related loss in binding of NF-κB and STAT factors. Thus, our study provides a unique and comprehensive approach to identifying candidate biomarkers and provides mechanistic insights into aging-associated immunodeficiency.

摘要

衰老与免疫反应缺陷及全身炎症增加有关。为了揭示这些变化背后的调控程序，我们应用了系统免疫学方法，并对外周血单核细胞（PBMC）以及纯化的单核细胞、B细胞和T细胞中的染色质可及性和转录组进行了分析。对77名年轻和老年捐赠者的样本分析揭示了PBMC中一种新的、强大的衰老特征，同时与T细胞信号传导相关的启动子和增强子处的染色质系统性关闭，以及主要在静止和抑制位点发现的潜在随机染色质开放。对染色质可及性和转录组的联合分析揭示了随衰老激活/失活的免疫分子，并确定该基因和IL-7信号通路基因的沉默为潜在生物标志物。这种特征由记忆CD8 T细胞呈现，其在NF-κB和STAT因子结合方面表现出与衰老相关的损失。因此，我们的研究提供了一种独特而全面的方法来识别候选生物标志物，并为衰老相关免疫缺陷提供了机制性见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c5c/5626401/cd5be9195aa6/JEM_20170416_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c5c/5626401/dea4de233a29/JEM_20170416_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c5c/5626401/0d5508a27ee9/JEM_20170416_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c5c/5626401/1cf69763b266/JEM_20170416_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c5c/5626401/d30373273f5f/JEM_20170416_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c5c/5626401/ceaeec3cc187/JEM_20170416_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c5c/5626401/b613f3d463f9/JEM_20170416_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c5c/5626401/cd5be9195aa6/JEM_20170416_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c5c/5626401/dea4de233a29/JEM_20170416_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c5c/5626401/0d5508a27ee9/JEM_20170416_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c5c/5626401/1cf69763b266/JEM_20170416_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c5c/5626401/d30373273f5f/JEM_20170416_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c5c/5626401/ceaeec3cc187/JEM_20170416_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c5c/5626401/b613f3d463f9/JEM_20170416_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c5c/5626401/cd5be9195aa6/JEM_20170416_Fig7.jpg

相似文献

1
The chromatin accessibility signature of human immune aging stems from CD8 T cells.人类免疫衰老的染色质可及性特征源于CD8 T细胞。
J Exp Med. 2017 Oct 2;214(10):3123-3144. doi: 10.1084/jem.20170416. Epub 2017 Sep 13.
2
Transcriptomic analysis of human IL-7 receptor alpha and effector memory CD8 T cells reveals an age-associated signature linked to influenza vaccine response in older adults.人类白细胞介素-7 受体α和效应记忆 CD8 T 细胞的转录组分析揭示了与老年人流感疫苗反应相关的与年龄相关的特征。
Aging Cell. 2019 Aug;18(4):e12960. doi: 10.1111/acel.12960. Epub 2019 May 1.
3
Elevated IFN-alpha/beta levels in a streptozotocin-induced type I diabetic mouse model promote oxidative stress and mediate depletion of spleen-homing CD8+ T cells by apoptosis through impaired CCL21/CCR7 axis and IL-7/CD127 signaling.在链脲佐菌素诱导的I型糖尿病小鼠模型中，升高的IFN-α/β水平会促进氧化应激，并通过受损的CCL21/CCR7轴和IL-7/CD127信号传导，介导脾脏归巢CD8+ T细胞通过凋亡而耗竭。
Cell Signal. 2015 Oct;27(10):2110-9. doi: 10.1016/j.cellsig.2015.07.005. Epub 2015 Jul 18.
4
Genome organization and chromatin analysis identify transcriptional downregulation of insulin-like growth factor signaling as a hallmark of aging in developing B cells.基因组组织和染色质分析确定胰岛素样生长因子信号的转录下调是发育中 B 细胞衰老的一个标志。
Genome Biol. 2018 Sep 5;19(1):126. doi: 10.1186/s13059-018-1489-y.
5
Reduced numbers of IL-7 receptor (CD127) expressing immune cells and IL-7-signaling defects in peripheral blood from patients with breast cancer.乳腺癌患者外周血中表达白细胞介素-7受体（CD127）的免疫细胞数量减少以及白细胞介素-7信号传导缺陷。
Int J Cancer. 2007 Oct 1;121(7):1512-9. doi: 10.1002/ijc.22854.
6
Differential role of lipid rafts in the functions of CD4+ and CD8+ human T lymphocytes with aging.脂筏在衰老的人CD4 +和CD8 + T淋巴细胞功能中的差异作用。
Cell Signal. 2006 Jul;18(7):1017-30. doi: 10.1016/j.cellsig.2005.08.016. Epub 2005 Oct 17.
7
CD8 T-cell immune phenotype of successful aging.成功衰老的CD8 T细胞免疫表型。
Mech Ageing Dev. 2006 Mar;127(3):231-9. doi: 10.1016/j.mad.2005.10.001. Epub 2005 Nov 28.
8
Defective CD8 Signaling Pathways Delay Rejection in Older Recipients.缺陷性CD8信号通路延迟老年受者的排斥反应。
Transplantation. 2016 Jan;100(1):69-79. doi: 10.1097/TP.0000000000000886.
9
Impaired CD8(+) T cell responses upon Toll-like receptor activation in common variable immunodeficiency.在常见可变免疫缺陷中，Toll样受体激活后CD8(+) T细胞反应受损。
J Transl Med. 2016 May 17;14(1):138. doi: 10.1186/s12967-016-0900-2.
10
Reference values for CD4+ and CD8+ T lymphocytes with naïve or memory phenotype and their association with mortality in the elderly.具有初始或记忆表型的CD4+和CD8+ T淋巴细胞的参考值及其与老年人死亡率的关联。
Gerontology. 2009;55(3):314-21. doi: 10.1159/000199451. Epub 2009 Feb 4.

引用本文的文献

1
Musculoskeletal biomarkers in health and disease: implications for the aging spine-a review for spinal surgeons by the SRS adult spinal deformity task force on senescence.健康与疾病中的肌肉骨骼生物标志物：对衰老脊柱的影响——脊柱侧凸研究学会成人脊柱畸形衰老问题特别工作组为脊柱外科医生撰写的综述
Spine Deform. 2025 Jun 4. doi: 10.1007/s43390-025-01124-w.
2
Meta-epigenetic shifts in T cell aging and aging-related dysfunction.T细胞衰老及衰老相关功能障碍中的元表观遗传变化。
J Biomed Sci. 2025 May 23;32(1):51. doi: 10.1186/s12929-025-01146-6.
3
Gut-vitamin D interplay: key to mitigating immunosenescence and promoting healthy ageing.

本文引用的文献

1
Chromatin states define tumour-specific T cell dysfunction and reprogramming.染色质状态决定肿瘤特异性T细胞功能障碍和重编程。
Nature. 2017 May 25;545(7655):452-456. doi: 10.1038/nature22367. Epub 2017 May 17.
2
Epigenomics of human CD8 T cell differentiation and aging.人类CD8 T细胞分化与衰老的表观基因组学
Sci Immunol. 2017 Feb;2(8). doi: 10.1126/sciimmunol.aag0192. Epub 2017 Feb 17.
3
Differential Effects of Environmental and Genetic Factors on T and B Cell Immune Traits.环境和遗传因素对T细胞和B细胞免疫特征的差异影响。
肠道与维生素D的相互作用：减轻免疫衰老和促进健康衰老的关键
Immun Ageing. 2025 May 19;22(1):20. doi: 10.1186/s12979-025-00514-y.
4
T Cell Aging: An Important Target for Perioperative Immunomodulation.T细胞衰老：围手术期免疫调节的重要靶点。
Clin Interv Aging. 2025 May 1;20:537-557. doi: 10.2147/CIA.S519438. eCollection 2025.
5
The single-cell immune landscape of HIV-associated aggressive B-cell lymphoma.人类免疫缺陷病毒相关侵袭性B细胞淋巴瘤的单细胞免疫图谱
J Natl Cancer Cent. 2025 Feb 12;5(2):221-235. doi: 10.1016/j.jncc.2025.02.001. eCollection 2025 Apr.
6
Single cell-resolved cellular, transcriptional, and epigenetic changes in mouse T cell populations linked to age-associated immune decline.与年龄相关的免疫衰退相关的小鼠T细胞群体中单细胞解析的细胞、转录和表观遗传变化。
Proc Natl Acad Sci U S A. 2025 Apr 8;122(14):e2425992122. doi: 10.1073/pnas.2425992122. Epub 2025 Mar 31.
7
FOXM1 expression reverts aging chromatin profiles through repression of the senescence-associated pioneer factor AP-1.FOXM1表达通过抑制衰老相关的先锋因子AP-1来逆转衰老染色质图谱。
Nat Commun. 2025 Mar 25;16(1):2931. doi: 10.1038/s41467-025-57503-4.
8
Metabolic Signaling as a Driver of T Cell Aging.代谢信号传导作为T细胞衰老的驱动因素
Immune Netw. 2025 Feb 24;25(1):e14. doi: 10.4110/in.2025.25.e14. eCollection 2025 Feb.
9
Molecular and Cellular Mechanisms of Immunosenescence: Modulation Through Interventions and Lifestyle Changes.免疫衰老的分子和细胞机制：通过干预措施和生活方式改变进行调节
Biology (Basel). 2024 Dec 27;14(1):17. doi: 10.3390/biology14010017.
10
Comprehensive single-cell aging atlas of healthy mammary tissues reveals shared epigenomic and transcriptomic signatures of aging and cancer.健康乳腺组织的综合单细胞衰老图谱揭示了衰老和癌症共有的表观基因组和转录组特征。
Nat Aging. 2025 Jan;5(1):122-143. doi: 10.1038/s43587-024-00751-8. Epub 2024 Nov 25.
Cell Rep. 2016 Nov 22;17(9):2474-2487. doi: 10.1016/j.celrep.2016.10.053. Epub 2016 Nov 3.
4
Host and Environmental Factors Influencing Individual Human Cytokine Responses.影响个体人类细胞因子反应的宿主和环境因素
Cell. 2016 Nov 3;167(4):1111-1124.e13. doi: 10.1016/j.cell.2016.10.018.
5
Epigenetics and aging.表观遗传学与衰老。
Sci Adv. 2016 Jul 29;2(7):e1600584. doi: 10.1126/sciadv.1600584. eCollection 2016 Jul.
6
Blood Epigenetic Age may Predict Cancer Incidence and Mortality.血液表观遗传年龄或可预测癌症发病率和死亡率。
EBioMedicine. 2016 Feb 8;5:68-73. doi: 10.1016/j.ebiom.2016.02.008. eCollection 2016 Mar.
7
Personalized Immunomonitoring Uncovers Molecular Networks that Stratify Lupus Patients.个性化免疫监测揭示了对狼疮患者进行分层的分子网络。
Cell. 2016 Apr 21;165(3):551-65. doi: 10.1016/j.cell.2016.03.008. Epub 2016 Mar 31.
8
Reduced naïve CD8(+) T-cell priming efficacy in elderly adults.老年人中初始CD8(+) T细胞致敏效力降低。
Aging Cell. 2016 Feb;15(1):14-21. doi: 10.1111/acel.12384. Epub 2015 Oct 15.
9
Single-cell RNA-seq reveals changes in cell cycle and differentiation programs upon aging of hematopoietic stem cells.单细胞RNA测序揭示了造血干细胞衰老过程中细胞周期和分化程序的变化。
Genome Res. 2015 Dec;25(12):1860-72. doi: 10.1101/gr.192237.115. Epub 2015 Oct 1.
10
Epigenetic regulation of ageing: linking environmental inputs to genomic stability.衰老的表观遗传调控：将环境输入与基因组稳定性相联系
Nat Rev Mol Cell Biol. 2015 Oct;16(10):593-610. doi: 10.1038/nrm4048. Epub 2015 Sep 16.