• 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

叉头框蛋白3（Foxp3）对调节性T细胞基因表达和功能的控制依赖于IKAROS。

Foxp3 depends on Ikaros for control of regulatory T cell gene expression and function.

作者信息

Thomas Rajan M, Pahl Matthew C, Wang Liqing, Grant Struan F A, Hancock Wayne W, Wells Andrew D

机构信息

Center for Spatial and Functional Genomics, The Children's Hospital of Philadelphia, Philadelphia, United States.

Department of Pathology, Perelman School of Medicine at the University of Pennsylvania and The Children's Hospital of Philadelphia, Philadelphia, United States.

出版信息

Elife. 2024 Apr 24;12:RP91392. doi: 10.7554/eLife.91392.

DOI:10.7554/eLife.91392
PMID:38655862
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11042806/
Abstract

Ikaros is a transcriptional factor required for conventional T cell development, differentiation, and anergy. While the related factors Helios and Eos have defined roles in regulatory T cells (Treg), a role for Ikaros has not been established. To determine the function of Ikaros in the Treg lineage, we generated mice with Treg-specific deletion of the Ikaros gene (). We find that Ikaros cooperates with Foxp3 to establish a major portion of the Treg epigenome and transcriptome. Ikaros-deficient Treg exhibit Th1-like gene expression with abnormal production of IL-2, IFNg, TNFa, and factors involved in Wnt and Notch signaling. While -Treg-cko mice do not develop spontaneous autoimmunity, Ikaros-deficient Treg are unable to control conventional T cell-mediated immune pathology in response to TCR and inflammatory stimuli in models of IBD and organ transplantation. These studies establish Ikaros as a core factor required in Treg for tolerance and the control of inflammatory immune responses.

摘要

Ikaros是传统T细胞发育、分化和无反应性所必需的转录因子。虽然相关因子Helios和Eos在调节性T细胞（Treg）中具有明确作用，但Ikaros的作用尚未明确。为了确定Ikaros在Treg谱系中的功能，我们构建了Ikaros基因在Treg中特异性缺失的小鼠。我们发现Ikaros与Foxp3协同作用，建立了Treg表观基因组和转录组的主要部分。Ikaros缺陷的Treg表现出Th1样基因表达，伴有IL-2、IFNg、TNFa以及Wnt和Notch信号通路相关因子的异常产生。虽然Treg-cko小鼠不会自发发生自身免疫，但在炎症性肠病和器官移植模型中，Ikaros缺陷的Treg在响应TCR和炎症刺激时无法控制传统T细胞介导的免疫病理。这些研究确定Ikaros是Treg中耐受和控制炎症性免疫反应所需的核心因子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7052/11042806/400830d2bce9/elife-91392-fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7052/11042806/b1171c7aab95/elife-91392-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7052/11042806/220c08ab467c/elife-91392-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7052/11042806/c4e6e5b5637a/elife-91392-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7052/11042806/4ea1ad255dff/elife-91392-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7052/11042806/cd5a37a19de9/elife-91392-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7052/11042806/5a8a6f208b27/elife-91392-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7052/11042806/0667543bb623/elife-91392-fig5-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7052/11042806/90fe38487b74/elife-91392-fig5-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7052/11042806/e3286e5cb730/elife-91392-fig5-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7052/11042806/50b24d5b4ee8/elife-91392-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7052/11042806/9d82542b4a9f/elife-91392-fig6-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7052/11042806/2dd132003f15/elife-91392-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7052/11042806/9e37c64e0e3c/elife-91392-fig7-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7052/11042806/9e4fb7cc5d92/elife-91392-fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7052/11042806/5f76c2becf54/elife-91392-fig8-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7052/11042806/ddc36f8b0ff0/elife-91392-fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7052/11042806/400830d2bce9/elife-91392-fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7052/11042806/b1171c7aab95/elife-91392-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7052/11042806/220c08ab467c/elife-91392-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7052/11042806/c4e6e5b5637a/elife-91392-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7052/11042806/4ea1ad255dff/elife-91392-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7052/11042806/cd5a37a19de9/elife-91392-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7052/11042806/5a8a6f208b27/elife-91392-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7052/11042806/0667543bb623/elife-91392-fig5-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7052/11042806/90fe38487b74/elife-91392-fig5-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7052/11042806/e3286e5cb730/elife-91392-fig5-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7052/11042806/50b24d5b4ee8/elife-91392-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7052/11042806/9d82542b4a9f/elife-91392-fig6-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7052/11042806/2dd132003f15/elife-91392-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7052/11042806/9e37c64e0e3c/elife-91392-fig7-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7052/11042806/9e4fb7cc5d92/elife-91392-fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7052/11042806/5f76c2becf54/elife-91392-fig8-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7052/11042806/ddc36f8b0ff0/elife-91392-fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7052/11042806/400830d2bce9/elife-91392-fig10.jpg

相似文献

1
Foxp3 depends on Ikaros for control of regulatory T cell gene expression and function.叉头框蛋白3（Foxp3）对调节性T细胞基因表达和功能的控制依赖于IKAROS。
Elife. 2024 Apr 24;12:RP91392. doi: 10.7554/eLife.91392.
2
Transcription factor Ikzf1 associates with Foxp3 to repress gene expression in Treg cells and limit autoimmunity and anti-tumor immunity.转录因子 Ikzf1 与 Foxp3 结合，抑制 Treg 细胞中的基因表达，从而限制自身免疫和抗肿瘤免疫。
Immunity. 2024 Sep 10;57(9):2043-2060.e10. doi: 10.1016/j.immuni.2024.07.010. Epub 2024 Aug 6.
3
CD4 regulatory T cells lacking Helios and Eos.缺乏Helios和Eos的CD4调节性T细胞。
Biochem Biophys Res Commun. 2023 Sep 24;674:83-89. doi: 10.1016/j.bbrc.2023.06.087. Epub 2023 Jun 28.
4
Foxp3+ Helios+ regulatory T cells are expanded in active systemic lupus erythematosus.Foxp3+Helios+调节性 T 细胞在活动性系统性红斑狼疮中扩增。
Ann Rheum Dis. 2013 Sep 1;72(9):1549-58. doi: 10.1136/annrheumdis-2012-202216. Epub 2012 Dec 21.
5
FoxP3, Helios, and SATB1: roles and relationships in regulatory T cells.FoxP3、Helios 和 SATB1：调节性 T 细胞中的作用和关系。
Int Immunopharmacol. 2013 Jul;16(3):343-7. doi: 10.1016/j.intimp.2013.02.004. Epub 2013 Feb 18.
6
Restriction of IL-22-producing T cell responses and differential regulation of regulatory T cell compartments by zinc finger transcription factor Ikaros.锌指转录因子Ikaros对产生白细胞介素-22的T细胞反应的限制及调节性T细胞亚群的差异调节
J Immunol. 2014 Oct 15;193(8):3934-46. doi: 10.4049/jimmunol.1401234. Epub 2014 Sep 5.
7
Selective deletion of Eos (Ikzf4) in T-regulatory cells leads to loss of suppressive function and development of systemic autoimmunity.选择性删除调节性 T 细胞中的 Eos（Ikzf4）可导致其抑制功能丧失和全身性自身免疫的发生。
J Autoimmun. 2019 Dec;105:102300. doi: 10.1016/j.jaut.2019.06.011. Epub 2019 Jul 8.
8
Helios Controls a Limited Subset of Regulatory T Cell Functions.太阳神控制调节性T细胞功能的有限子集。
J Immunol. 2016 Jan 1;196(1):144-55. doi: 10.4049/jimmunol.1501704. Epub 2015 Nov 18.
9
Foxp3+ Treg expanded from patients with established diabetes reduce Helios expression while retaining normal function compared to healthy individuals.与健康个体相比，从已确诊糖尿病患者中扩增的 Foxp3+ Treg 细胞表达降低，而保留正常功能。
PLoS One. 2013;8(2):e56209. doi: 10.1371/journal.pone.0056209. Epub 2013 Feb 11.
10
Regulatory T Cells from Patients with Rheumatoid Arthritis Are Characterized by Reduced Expression of Ikaros Zinc Finger Transcription Factors.类风湿关节炎患者调节性 T 细胞的特征是 Ikaros 锌指转录因子表达减少。
Cells. 2022 Jul 11;11(14):2171. doi: 10.3390/cells11142171.

引用本文的文献

1
Cis-Regulatory Element and Transcription Factor Circuitry Required for Cell-Type Specific Expression of FOXP3.FOXP3细胞类型特异性表达所需的顺式调控元件和转录因子调控网络
bioRxiv. 2025 Jan 14:2024.08.30.610436. doi: 10.1101/2024.08.30.610436.

本文引用的文献

1
Ikaros-Associated Diseases: From Mice to Humans and Back Again.与伊卡洛斯相关的疾病：从小鼠到人类，再回归小鼠
Front Pediatr. 2021 Jul 16;9:705497. doi: 10.3389/fped.2021.705497. eCollection 2021.
2
Ikaros antagonizes DNA binding by STAT5 in pre-B cells.Ikaros 拮抗 pre-B 细胞中 STAT5 的 DNA 结合。
PLoS One. 2020 Nov 12;15(11):e0242211. doi: 10.1371/journal.pone.0242211. eCollection 2020.
3
MEF2D sustains activation of effector Foxp3+ Tregs during transplant survival and anticancer immunity.MEF2D 在移植存活和抗肿瘤免疫过程中维持效应性 Foxp3+ Treg 的激活。
J Clin Invest. 2020 Dec 1;130(12):6242-6260. doi: 10.1172/JCI135486.
4
Mapping effector genes at lupus GWAS loci using promoter Capture-C in follicular helper T cells.利用启动子捕获技术在滤泡辅助性 T 细胞中定位狼疮 GWAS 位点的效应基因。
Nat Commun. 2020 Jul 3;11(1):3294. doi: 10.1038/s41467-020-17089-5.
5
Treg Heterogeneity, Function, and Homeostasis.调节性 T 细胞异质性、功能和稳态。
Front Immunol. 2020 Jan 14;10:3100. doi: 10.3389/fimmu.2019.03100. eCollection 2019.
6
JASPAR 2020: update of the open-access database of transcription factor binding profiles.JASPAR 2020：转录因子结合谱开放获取数据库的更新。
Nucleic Acids Res. 2020 Jan 8;48(D1):D87-D92. doi: 10.1093/nar/gkz1001.
7
Selective deletion of Eos (Ikzf4) in T-regulatory cells leads to loss of suppressive function and development of systemic autoimmunity.选择性删除调节性 T 细胞中的 Eos（Ikzf4）可导致其抑制功能丧失和全身性自身免疫的发生。
J Autoimmun. 2019 Dec;105:102300. doi: 10.1016/j.jaut.2019.06.011. Epub 2019 Jul 8.
8
Tcf1 and Lef1 are required for the immunosuppressive function of regulatory T cells.Tcf1 和 Lef1 对于调节性 T 细胞的免疫抑制功能是必需的。
J Exp Med. 2019 Apr 1;216(4):847-866. doi: 10.1084/jem.20182010. Epub 2019 Mar 5.
9
Activated β-catenin in Foxp3 regulatory T cells links inflammatory environments to autoimmunity.Foxp3 调节性 T 细胞中的活化β-连环蛋白将炎症环境与自身免疫联系起来。
Nat Immunol. 2018 Dec;19(12):1391-1402. doi: 10.1038/s41590-018-0236-6. Epub 2018 Oct 29.
10
Characterization of Blimp-1 function in effector regulatory T cells.鉴定效应调节性 T 细胞中 Blimp-1 的功能。
J Autoimmun. 2018 Jul;91:73-82. doi: 10.1016/j.jaut.2018.04.003. Epub 2018 Apr 30.