• 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

IL-35 通过维持 CCR5 扩增的 Treg 抑制机制促进 CD4+Foxp3+Tregs 的生成并抑制动脉粥样硬化。

IL-35 promotes CD4+Foxp3+ Tregs and inhibits atherosclerosis via maintaining CCR5-amplified Treg-suppressive mechanisms.

机构信息

Centers for Cardiovascular Research.

Metabolic Disease Research & Thrombosis Research, Department of Cardiovascular Sciences, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, USA.

出版信息

JCI Insight. 2021 Oct 8;6(19):e152511. doi: 10.1172/jci.insight.152511.

DOI:10.1172/jci.insight.152511
PMID:34622804
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8525592/
Abstract

Tregs play vital roles in suppressing atherogenesis. Pathological conditions reshape Tregs and increase Treg-weakening plasticity. It remains unclear how Tregs preserve their function and how Tregs switch into alternative phenotypes in the environment of atherosclerosis. In this study, we observed a great induction of CD4+Foxp3+ Tregs in the spleen and aorta of ApoE-/- mice, accompanied by a significant increase of plasma IL-35 levels. To determine if IL-35 devotes its role in the rise of Tregs, we generated IL-35 subunit P35-deficient (IL-35P35-deficient) mice on an ApoE-/- background and found Treg reduction in the spleen and aorta compared with ApoE-/- controls. In addition, our RNA sequencing data show the elevation of a set of chemokine receptor transcripts in the ApoE-/- Tregs, and we have validated higher CCR5 expression in ApoE-/- Tregs in the presence of IL-35 than in the absence of IL-35. Furthermore, we observed that CCR5+ Tregs in ApoE-/- have lower Treg-weakening AKT-mTOR signaling, higher expression of inhibitory checkpoint receptors TIGIT and PD-1, and higher expression of IL-10 compared with WT CCR5+ Tregs. In conclusion, IL-35 counteracts hyperlipidemia in maintaining Treg-suppressive function by increasing 3 CCR5-amplified mechanisms, including Treg migration, inhibition of Treg weakening AKT-mTOR signaling, and promotion of TIGIT and PD-1 signaling.

摘要

调节性 T 细胞（Tregs）在抑制动脉粥样硬化形成中发挥着重要作用。病理条件重塑了 Tregs 并增加了 Treg 弱化的可塑性。目前尚不清楚 Tregs 如何维持其功能，以及 Tregs 在动脉粥样硬化环境中如何转变为替代表型。在这项研究中，我们观察到 ApoE-/- 小鼠脾脏和主动脉中 CD4+Foxp3+ Tregs 的大量诱导，同时血浆 IL-35 水平显著升高。为了确定 IL-35 是否在 Tregs 的增加中发挥作用，我们在 ApoE-/- 背景下生成了缺乏 IL-35 亚单位 P35（IL-35P35-deficient）的小鼠，并发现与 ApoE-/- 对照组相比，脾脏和主动脉中的 Treg 减少。此外，我们的 RNA 测序数据显示 ApoE-/- Tregs 中一组趋化因子受体转录本的升高，并且我们已经验证了在存在 IL-35 的情况下，ApoE-/- Tregs 中 CCR5 的表达高于不存在 IL-35 的情况下。此外，我们观察到 ApoE-/- 中的 CCR5+Tregs 具有较低的 Treg 弱化 AKT-mTOR 信号，更高的抑制性检查点受体 TIGIT 和 PD-1 的表达，以及更高的 IL-10 表达，与 WT CCR5+Tregs 相比。总之，IL-35 通过增加 3 个 CCR5 扩增机制来对抗高脂血症，从而维持 Treg 的抑制功能，包括 Treg 迁移、抑制 Treg 弱化 AKT-mTOR 信号以及促进 TIGIT 和 PD-1 信号。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d547/8525592/82449838aeb7/jciinsight-6-152511-g243.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d547/8525592/1e6e63977f05/jciinsight-6-152511-g241.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d547/8525592/d5da2d4162e6/jciinsight-6-152511-g244.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d547/8525592/e9dc6c00eb30/jciinsight-6-152511-g245.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d547/8525592/b1e44cbb5363/jciinsight-6-152511-g246.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d547/8525592/e4b6a7c9b8a6/jciinsight-6-152511-g247.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d547/8525592/86d2a11d39ed/jciinsight-6-152511-g248.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d547/8525592/9ece23cf08a9/jciinsight-6-152511-g249.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d547/8525592/f1873928e58e/jciinsight-6-152511-g250.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d547/8525592/4ace5a8e09a1/jciinsight-6-152511-g251.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d547/8525592/b4bca574b6b4/jciinsight-6-152511-g242.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d547/8525592/82449838aeb7/jciinsight-6-152511-g243.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d547/8525592/1e6e63977f05/jciinsight-6-152511-g241.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d547/8525592/d5da2d4162e6/jciinsight-6-152511-g244.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d547/8525592/e9dc6c00eb30/jciinsight-6-152511-g245.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d547/8525592/b1e44cbb5363/jciinsight-6-152511-g246.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d547/8525592/e4b6a7c9b8a6/jciinsight-6-152511-g247.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d547/8525592/86d2a11d39ed/jciinsight-6-152511-g248.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d547/8525592/9ece23cf08a9/jciinsight-6-152511-g249.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d547/8525592/f1873928e58e/jciinsight-6-152511-g250.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d547/8525592/4ace5a8e09a1/jciinsight-6-152511-g251.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d547/8525592/b4bca574b6b4/jciinsight-6-152511-g242.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d547/8525592/82449838aeb7/jciinsight-6-152511-g243.jpg

相似文献

1
IL-35 promotes CD4+Foxp3+ Tregs and inhibits atherosclerosis via maintaining CCR5-amplified Treg-suppressive mechanisms.IL-35 通过维持 CCR5 扩增的 Treg 抑制机制促进 CD4+Foxp3+Tregs 的生成并抑制动脉粥样硬化。
JCI Insight. 2021 Oct 8;6(19):e152511. doi: 10.1172/jci.insight.152511.
2
CCR5 ameliorates Japanese encephalitis via dictating the equilibrium of regulatory CD4(+)Foxp3(+) T and IL-17(+)CD4(+) Th17 cells.CCR5通过调控调节性CD4(+)Foxp3(+)T细胞和IL-17(+)CD4(+)Th17细胞之间的平衡来改善日本脑炎。
J Neuroinflammation. 2016 Jul 20;13(1):223. doi: 10.1186/s12974-016-0656-x.
3
Atherosclerosis-Driven Treg Plasticity Results in Formation of a Dysfunctional Subset of Plastic IFNγ+ Th1/Tregs.动脉粥样硬化驱动的调节性T细胞可塑性导致形成功能失调的可塑性IFNγ+ Th1/调节性T细胞亚群。
Circ Res. 2016 Nov 11;119(11):1190-1203. doi: 10.1161/CIRCRESAHA.116.309764. Epub 2016 Sep 15.
4
Acceleratory effects of ambient fine particulate matter on the development and progression of atherosclerosis in apolipoprotein E knockout mice by down-regulating CD4CD25Foxp3 regulatory T cells.环境细颗粒物通过下调 CD4CD25Foxp3 调节性 T 细胞加速载脂蛋白 E 基因敲除小鼠动脉粥样硬化的发生发展。
Toxicol Lett. 2019 Nov;316:27-34. doi: 10.1016/j.toxlet.2019.09.005. Epub 2019 Sep 9.
5
CCR5+T-bet+FoxP3+ Effector CD4 T Cells Drive Atherosclerosis.CCR5+T-bet+FoxP3+效应性CD4 T细胞驱动动脉粥样硬化。
Circ Res. 2016 May 13;118(10):1540-52. doi: 10.1161/CIRCRESAHA.116.308648. Epub 2016 Mar 28.
6
Changes in CD4CD25 Tregs in the pathogenesis of atherosclerosis in ApoE mice.载脂蛋白E基因敲除小鼠动脉粥样硬化发病机制中CD4CD25调节性T细胞的变化
Exp Biol Med (Maywood). 2017 May;242(9):918-925. doi: 10.1177/1535370216689826. Epub 2017 Jan 1.
7
Role of naturally occurring CD4+ CD25+ regulatory T cells in experimental atherosclerosis.天然存在的CD4+CD25+调节性T细胞在实验性动脉粥样硬化中的作用。
Arterioscler Thromb Vasc Biol. 2007 Apr;27(4):893-900. doi: 10.1161/01.ATV.0000259365.31469.89. Epub 2007 Feb 1.
8
Tumor Progression Locus 2 (Tpl2) Activates the Mammalian Target of Rapamycin (mTOR) Pathway, Inhibits Forkhead Box P3 (FoxP3) Expression, and Limits Regulatory T Cell (Treg) Immunosuppressive Functions.肿瘤进展位点2（Tpl2）激活雷帕霉素哺乳动物靶标（mTOR）通路，抑制叉头框蛋白P3（FoxP3）表达，并限制调节性T细胞（Treg）的免疫抑制功能。
J Biol Chem. 2016 Aug 5;291(32):16802-15. doi: 10.1074/jbc.M116.718783. Epub 2016 Jun 3.
9
IL-6 alters migration capacity of CD4Foxp3 regulatory T cells in systemic lupus erythematosus.白细胞介素 6 改变系统性红斑狼疮中 CD4Foxp3 调节性 T 细胞的迁移能力。
Scand J Immunol. 2021 Nov;94(5):e13099. doi: 10.1111/sji.13099. Epub 2021 Sep 8.
10
[Proliferation of CD4+ CD25+ regulatory T cells of rat by different cytokines in vitro].[不同细胞因子体外诱导大鼠CD4+ CD25+调节性T细胞增殖的研究]
Zhonghua Yi Xue Za Zhi. 2008 Mar 25;88(12):844-7.

引用本文的文献

1
How lactate and lactylation shape the immunity system in atherosclerosis (Review).乳酸和乳酰化如何塑造动脉粥样硬化中的免疫系统（综述）。
Int J Mol Med. 2025 Oct;56(4). doi: 10.3892/ijmm.2025.5604. Epub 2025 Aug 1.
2
Interleukin-35 impairs human NK cell effector functions and induces their ILC1-like conversion with tissue residency features.白细胞介素-35损害人类自然杀伤细胞的效应功能，并诱导其向具有组织驻留特征的1型固有淋巴细胞样转化。
Nat Commun. 2025 Jul 3;16(1):6135. doi: 10.1038/s41467-025-61196-0.
3
Pro-Resolving Macrophage-Induced IL-35 but Not TGF-β1 Regulatory B Cell Activation Requires the PD-L1/PD-1 Pathway.

本文引用的文献

1
Tissue Treg Secretomes and Transcription Factors Shared With Stem Cells Contribute to a Treg Niche to Maintain Treg-Ness With 80% Innate Immune Pathways, and Functions of Immunosuppression and Tissue Repair.组织 Treg 分泌组和与干细胞共享的转录因子有助于形成 Treg 生态位，维持 Treg 特性，其中 80%为固有免疫途径，并具有免疫抑制和组织修复功能。
Front Immunol. 2021 Feb 5;11:632239. doi: 10.3389/fimmu.2020.632239. eCollection 2020.
2
CTLA-4 blockade drives loss of T stability in glycolysis-low tumours.CTLA-4 阻断导致糖酵解低下肿瘤中 T 细胞稳定性丧失。
Nature. 2021 Mar;591(7851):652-658. doi: 10.1038/s41586-021-03326-4. Epub 2021 Feb 15.
3
促分解巨噬细胞诱导的IL-35而非TGF-β1调节性B细胞激活需要PD-L1/PD-1途径。
Int J Mol Sci. 2025 Jun 1;26(11):5332. doi: 10.3390/ijms26115332.
4
IL-35 Ameliorates Myocardial Strain in Mice with T2DM-Induced Cardiac Injury: Assessment by Layer-Specific Strain.白细胞介素-35改善2型糖尿病诱导的心脏损伤小鼠的心肌应变：通过分层特异性应变评估
Diabetes Metab Syndr Obes. 2025 May 10;18:1551-1562. doi: 10.2147/DMSO.S510594. eCollection 2025.
5
Lidocaine Modulates Cytokine Production and Reprograms the Tumor Immune Microenvironment to Enhance Anti-Tumor Immune Responses in Gastric Cancer.利多卡因调节细胞因子产生并重塑肿瘤免疫微环境以增强胃癌的抗肿瘤免疫反应。
Int J Mol Sci. 2025 Mar 31;26(7):3236. doi: 10.3390/ijms26073236.
6
Alzheimer's disease as an auto-innate immune pathology with potential cell trans-differentiation and enhanced trained immunity in 3xTg-AD mouse model.在3xTg-AD小鼠模型中，阿尔茨海默病作为一种具有潜在细胞转分化和增强训练免疫的自身固有免疫病理学。
J Alzheimers Dis. 2025 May;105(2):550-572. doi: 10.1177/13872877251329583. Epub 2025 Apr 15.
7
The dual role of tissue regulatory T cells in tissue repair: return to homeostasis or fibrosis.组织调节性T细胞在组织修复中的双重作用：恢复内稳态还是纤维化。
Front Immunol. 2025 Mar 6;16:1560578. doi: 10.3389/fimmu.2025.1560578. eCollection 2025.
8
Systematic Review of Interleukin-35 in Endothelial Dysfunction: A New Target for Therapeutic Intervention.内皮功能障碍中白细胞介素-35的系统评价：治疗干预的新靶点
Mediators Inflamm. 2025 Feb 12;2025:2003124. doi: 10.1155/mi/2003124. eCollection 2025.
9
Immune Checkpoints Are New Therapeutic Targets in Regulating Cardio-, and Cerebro-Vascular Diseases and CD4Foxp3 Regulatory T Cell Immunosuppression.免疫检查点是调节心脑血管疾病和CD4Foxp3调节性T细胞免疫抑制的新治疗靶点。
Int J Drug Discov Pharm. 2024 Dec;3(4). doi: 10.53941/ijddp.2024.100022. Epub 2024 Nov 26.
10
Annexin A8 deficiency delays atherosclerosis progression.膜联蛋白A8缺乏会延缓动脉粥样硬化的进展。
Clin Transl Med. 2025 Jan;15(1):e70176. doi: 10.1002/ctm2.70176.
AIM2 in regulatory T cells restrains autoimmune diseases.
AIM2 在调节性 T 细胞中抑制自身免疫性疾病。
Nature. 2021 Mar;591(7849):300-305. doi: 10.1038/s41586-021-03231-w. Epub 2021 Jan 27.
4
Interleukin 35 Delays Hindlimb Ischemia-Induced Angiogenesis Through Regulating ROS-Extracellular Matrix but Spares Later Regenerative Angiogenesis.白细胞介素 35 通过调节 ROS-细胞外基质延迟后肢缺血诱导的血管生成，但不影响后期再生血管生成。
Front Immunol. 2020 Oct 14;11:595813. doi: 10.3389/fimmu.2020.595813. eCollection 2020.
5
Pathogenic Autoimmunity in Atherosclerosis Evolves From Initially Protective Apolipoprotein B-Reactive CD4 T-Regulatory Cells.动脉粥样硬化中的致病性自身免疫源于最初保护性的载脂蛋白 B 反应性 CD4 T 调节细胞。
Circulation. 2020 Sep 29;142(13):1279-1293. doi: 10.1161/CIRCULATIONAHA.119.042863. Epub 2020 Jul 24.
6
Vascular Endothelial Cells and Innate Immunity.血管内皮细胞与先天免疫
Arterioscler Thromb Vasc Biol. 2020 Jun;40(6):e138-e152. doi: 10.1161/ATVBAHA.120.314330. Epub 2020 May 27.
7
CCL11 increases the proportion of CD4+CD25+Foxp3+ Treg cells and the production of IL‑2 and TGF‑β by CD4+ T cells via the STAT5 signaling pathway.CCL11 通过 STAT5 信号通路增加 CD4+CD25+Foxp3+Treg 细胞的比例和 CD4+T 细胞产生的 IL-2 和 TGF-β。
Mol Med Rep. 2020 Jun;21(6):2522-2532. doi: 10.3892/mmr.2020.11049. Epub 2020 Apr 1.
8
Modulation of regulatory T cell function and stability by co-inhibitory receptors.共抑制受体对调节性 T 细胞功能和稳定性的调节。
Nat Rev Immunol. 2020 Nov;20(11):680-693. doi: 10.1038/s41577-020-0296-3. Epub 2020 Apr 8.
9
Co-expression of master transcription factors determines CD4 T cell plasticity and functions in auto-inflammatory diseases.主转录因子的共表达决定了 CD4 T 细胞在自身炎症性疾病中的可塑性和功能。
Immunol Lett. 2020 Jun;222:58-66. doi: 10.1016/j.imlet.2020.03.007. Epub 2020 Mar 24.
10
T cell subsets and functions in atherosclerosis.T 细胞亚群及其在动脉粥样硬化中的功能。
Nat Rev Cardiol. 2020 Jul;17(7):387-401. doi: 10.1038/s41569-020-0352-5. Epub 2020 Mar 16.