• 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

CD86 和 IL-12p70 是 Toll 样受体诱导的树突状细胞激活 T 辅助 1 极化和自然杀伤细胞的关键因素。

CD86 and IL-12p70 are key players for T helper 1 polarization and natural killer cell activation by Toll-like receptor-induced dendritic cells.

机构信息

Department of Internal Medicine III, Klinikum der Universität München, Munich, Germany.

出版信息

PLoS One. 2012;7(9):e44266. doi: 10.1371/journal.pone.0044266. Epub 2012 Sep 4.

DOI:10.1371/journal.pone.0044266
PMID:22962607
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3433478/
Abstract

BACKGROUND

Dendritic cells (DCs) determine the activation and polarization of T cells via expression of costimulatory molecules and secretion of cytokines. The function of DCs derived from monocytes ex vivo strongly depends on the composition of the maturation cocktail used.

METHODOLOGY/PRINCIPAL FINDINGS: We analyzed the effect of costimulatory molecule expression and cytokine secretion by DCs on T and natural killer (NK) cell activation by conducting a head-to-head comparison of a Toll-like receptor (TLR) agonist-based cocktail with the standard combination of proinflammatory cytokines or IL-10 alone. We could show that TLR-induced DCs are characterized by a predominance of costimulatory over coinhibitory molecules and by high secretion of IL-12p70, but not IL-10. Functionally, these signals translated into an increase in IFN-γ secreting Th1 cells and a decrease in regulatory T cells. T cell activation and polarization were dependent on IL-12p70 and CD86, but remarkably not on CD80 signaling. By means of IL-12p70 secretion, only TLR-induced DCs activated NK cells.

CONCLUSIONS/SIGNIFICANCE: TLR-matured DCs are highly suitable for application in immunotherapeutic strategies that rely on strong type 1 polarization and NK cell activation. Their effects particularly depend on high CD86 expression and IL-12p70 secretion.

摘要

背景

树突状细胞 (DCs) 通过表达共刺激分子和分泌细胞因子来决定 T 细胞的激活和极化。体外来源于单核细胞的 DCs 的功能强烈依赖于所用成熟鸡尾酒的组成。

方法/主要发现：我们通过对 Toll 样受体 (TLR) 激动剂为基础的鸡尾酒与单独使用促炎细胞因子或 IL-10 的标准组合进行头对头比较，分析了 DCs 上共刺激分子表达和细胞因子分泌对 T 和自然杀伤 (NK) 细胞激活的影响。我们可以证明 TLR 诱导的 DCs 的特征是共刺激分子超过共抑制分子的优势，并且高分泌 IL-12p70，但不分泌 IL-10。功能上，这些信号转化为 IFN-γ 分泌 Th1 细胞增加和调节性 T 细胞减少。T 细胞的激活和极化依赖于 IL-12p70 和 CD86，但令人惊讶的是不依赖于 CD80 信号。通过 IL-12p70 分泌，只有 TLR 诱导的 DCs 能激活 NK 细胞。

结论/意义：TLR 成熟的 DCs 非常适合应用于依赖于强烈的 1 型极化和 NK 细胞激活的免疫治疗策略。它们的作用特别取决于高 CD86 表达和 IL-12p70 分泌。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e73/3433478/b509c1c5b6e4/pone.0044266.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e73/3433478/e4ab0718f762/pone.0044266.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e73/3433478/10d9765029f1/pone.0044266.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e73/3433478/007f241a4611/pone.0044266.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e73/3433478/2965e542d995/pone.0044266.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e73/3433478/0bca0927f4a0/pone.0044266.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e73/3433478/b509c1c5b6e4/pone.0044266.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e73/3433478/e4ab0718f762/pone.0044266.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e73/3433478/10d9765029f1/pone.0044266.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e73/3433478/007f241a4611/pone.0044266.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e73/3433478/2965e542d995/pone.0044266.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e73/3433478/0bca0927f4a0/pone.0044266.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e73/3433478/b509c1c5b6e4/pone.0044266.g006.jpg

相似文献

1
CD86 and IL-12p70 are key players for T helper 1 polarization and natural killer cell activation by Toll-like receptor-induced dendritic cells.CD86 和 IL-12p70 是 Toll 样受体诱导的树突状细胞激活 T 辅助 1 极化和自然杀伤细胞的关键因素。
PLoS One. 2012;7(9):e44266. doi: 10.1371/journal.pone.0044266. Epub 2012 Sep 4.
2
Helper activity of natural killer cells during the dendritic cell-mediated induction of melanoma-specific cytotoxic T cells.树突状细胞介导的黑色素瘤特异性细胞毒性 T 细胞诱导过程中自然杀伤细胞的辅助活性。
J Immunother. 2011 Apr;34(3):270-8. doi: 10.1097/CJI.0b013e31820b370b.
3
Potency of Both Human Th1 and NK Helper Cell Activation is Determined by IL-12p70-Producing PAMP-Matured DCs.人Th1细胞和NK辅助细胞的激活效力由产生IL-12p70的模式识别受体成熟的树突状细胞决定。
J Interferon Cytokine Res. 2015 Sep;35(9):748-58. doi: 10.1089/jir.2015.0022. Epub 2015 Jul 2.
4
Generation of human dendritic cells that simultaneously secrete IL-12 and have migratory capacity by adenoviral gene transfer of hCD40L in combination with IFN-gamma.通过腺病毒介导的hCD40L基因与γ干扰素共转染，生成同时分泌白细胞介素-12并具有迁移能力的人树突状细胞。
J Immunother. 2009 Jun;32(5):524-38. doi: 10.1097/CJI.0b013e3181a28422.
5
mTOR and GSK-3 shape the CD4+ T-cell stimulatory and differentiation capacity of myeloid DCs after exposure to LPS.脂多糖作用后 mTOR 和 GSK-3 调节树突状细胞刺激 CD4+T 细胞的能力和分化。
Blood. 2010 Jun 10;115(23):4758-69. doi: 10.1182/blood-2009-10-251488. Epub 2010 Mar 24.
6
Uncarinic acid C plus IFN-γ generates monocyte-derived dendritic cells and induces a potent Th1 polarization with capacity to migrate.乌卡瑞替酸 C 联合 IFN-γ 可诱导单核细胞来源的树突状细胞分化，并诱导具有迁移能力的强 Th1 极化。
Cell Immunol. 2010;266(1):104-10. doi: 10.1016/j.cellimm.2010.09.004. Epub 2010 Sep 18.
7
C1q enhances IFN-gamma production by antigen-specific T cells via the CD40 costimulatory pathway on dendritic cells.C1q通过树突状细胞上的CD40共刺激途径增强抗原特异性T细胞产生γ干扰素。
Blood. 2009 Apr 9;113(15):3485-93. doi: 10.1182/blood-2008-06-164392. Epub 2009 Jan 26.
8
Generation of clinical grade dendritic cells with capacity to produce biologically active IL-12p70.生成具有产生生物活性IL-12p70能力的临床级树突状细胞。
J Transl Med. 2007 Apr 12;5:18. doi: 10.1186/1479-5876-5-18.
9
Toll-like receptor (TLR)2 and TLR3 synergy and cross-inhibition in murine myeloid dendritic cells.小鼠髓样树突状细胞中Toll样受体（TLR）2和TLR3的协同作用及交叉抑制
Immunol Lett. 2008 Feb 15;116(1):86-94. doi: 10.1016/j.imlet.2007.11.014. Epub 2007 Dec 17.
10
Polarization of naive T cells into Th1 or Th2 by distinct cytokine-driven murine dendritic cell populations: implications for immunotherapy.不同细胞因子驱动的小鼠树突状细胞群体将初始T细胞极化为Th1或Th2细胞：对免疫治疗的启示。
J Leukoc Biol. 2005 Sep;78(3):656-64. doi: 10.1189/jlb.1104631. Epub 2005 Jun 16.

引用本文的文献

1
TLR7-Adjuvanted Ionizable Lipid Nanoparticles for mRNA Vaccine Delivery.用于mRNA疫苗递送的TLR7佐剂可电离脂质纳米颗粒
AAPS J. 2025 Apr 25;27(4):80. doi: 10.1208/s12248-025-01073-2.
2
Beyond Adaptive Immunity: Trained Innate Immune Responses as a Novel Frontier in Hepatocellular Carcinoma Therapy.超越适应性免疫：训练有素的先天免疫反应作为肝细胞癌治疗的新前沿
Cancers (Basel). 2025 Apr 7;17(7):1250. doi: 10.3390/cancers17071250.
3
Adipose tissue from oesophageal adenocarcinoma patients is differentially affected by chemotherapy and chemoradiotherapy regimens altering immune cell phenotype and cancer cell metabolism.

本文引用的文献

1
Dendritic cells: indispensable?树突状细胞：不可或缺？
Cancer J. 2011 Sep-Oct;17(5):337-42. doi: 10.1097/PPO.0b013e3182350077.
2
Effects of TLR agonists on maturation and function of 3-day dendritic cells from AML patients in complete remission.TLR 激动剂对完全缓解的 AML 患者 3 天树突状细胞成熟和功能的影响。
J Transl Med. 2011 Sep 13;9:151. doi: 10.1186/1479-5876-9-151.
3
Engineering dendritic cells to enhance cancer immunotherapy.工程化树突状细胞以增强癌症免疫疗法。
来自食管腺癌患者的脂肪组织受化疗和放化疗方案的影响不同，这些方案会改变免疫细胞表型和癌细胞代谢。
Transl Oncol. 2025 Mar;53:102302. doi: 10.1016/j.tranon.2025.102302. Epub 2025 Feb 17.
4
The immune microenvironment of cancer of the uterine cervix.宫颈癌的免疫微环境。
Histol Histopathol. 2024 Oct;39(10):1245-1271. doi: 10.14670/HH-18-727. Epub 2024 Mar 1.
5
Cytokine profile in first-episode drug-naïve major depressive disorder patients with or without anxiety.首发未用药的伴或不伴焦虑的重性抑郁障碍患者的细胞因子谱。
BMC Psychiatry. 2024 Feb 2;24(1):93. doi: 10.1186/s12888-024-05536-2.
6
Integrated analysis reveals the potential of cluster of differentiation 86 as a key biomarker in high-grade glioma.综合分析揭示了分化群 86 作为高级别神经胶质瘤关键生物标志物的潜力。
Aging (Albany NY). 2023 Dec 26;15(24):15402-15418. doi: 10.18632/aging.205359.
7
Combinations of Toll-like receptor 8 agonist TL8-506 activate human tumor-derived dendritic cells.TL8-506 型 Toll 样受体 8 激动剂联合应用激活人源肿瘤源性树突状细胞。
J Immunother Cancer. 2022 Jun;10(6). doi: 10.1136/jitc-2021-004268.
8
Fusion of Bacterial Flagellin to a Dendritic Cell-Targeting αCD40 Antibody Construct Coupled With Viral or Leukemia-Specific Antigens Enhances Dendritic Cell Maturation and Activates Peptide-Responsive T Cells.细菌鞭毛蛋白与靶向树突状细胞的 αCD40 抗体构建体融合，与病毒或白血病特异性抗原偶联，可增强树突状细胞的成熟并激活肽反应性 T 细胞。
Front Immunol. 2020 Nov 12;11:602802. doi: 10.3389/fimmu.2020.602802. eCollection 2020.
9
Oncolytic adenovirus ORCA-010 increases the type 1 T cell stimulatory capacity of melanoma-conditioned dendritic cells.溶瘤腺病毒 ORCA-010 增强了黑色素瘤条件化树突状细胞的 1 型 T 细胞刺激能力。
Clin Exp Immunol. 2020 Aug;201(2):145-160. doi: 10.1111/cei.13442. Epub 2020 May 6.
10
Toll-like receptor 7/8-matured RNA-transduced dendritic cells as post-remission therapy in acute myeloid leukaemia: results of a phase I trial.Toll样受体7/8成熟RNA转导的树突状细胞作为急性髓系白血病缓解后治疗：一项I期试验的结果
Clin Transl Immunology. 2020 Mar 3;9(3):e1117. doi: 10.1002/cti2.1117. eCollection 2020.
Mol Ther. 2011 May;19(5):841-53. doi: 10.1038/mt.2011.57. Epub 2011 Apr 5.
4
Harnessing dendritic cells in cancer.利用树突状细胞治疗癌症。
Semin Immunol. 2011 Feb;23(1):42-9. doi: 10.1016/j.smim.2011.01.003. Epub 2011 Feb 3.
5
Dendritic cell vaccination in combination with anti-CD25 monoclonal antibody treatment: a phase I/II study in metastatic melanoma patients.树突状细胞疫苗接种联合抗 CD25 单克隆抗体治疗：转移性黑色素瘤患者的 I/II 期研究。
Clin Cancer Res. 2010 Oct 15;16(20):5067-78. doi: 10.1158/1078-0432.CCR-10-1757. Epub 2010 Aug 24.
6
Human myeloid dendritic cells for cancer therapy: does maturation matter?人类髓系树突状细胞在癌症治疗中的应用：成熟度重要吗？
Vaccine. 2010 Jul 19;28(32):5153-60. doi: 10.1016/j.vaccine.2010.05.042.
7
Induction of complete and molecular remissions in acute myeloid leukemia by Wilms' tumor 1 antigen-targeted dendritic cell vaccination.通过针对 Wilms 瘤 1 抗原的树突状细胞疫苗接种诱导急性髓细胞白血病的完全和分子缓解。
Proc Natl Acad Sci U S A. 2010 Aug 3;107(31):13824-9. doi: 10.1073/pnas.1008051107. Epub 2010 Jul 14.
8
Generation of Th1-polarizing dendritic cells using the TLR7/8 agonist CL075.利用 TLR7/8 激动剂 CL075 生成 Th1 极化树突状细胞。
J Immunol. 2010 Jul 1;185(1):738-47. doi: 10.4049/jimmunol.1000060. Epub 2010 May 28.
9
Increased regulatory T-cell frequencies in patients with advanced melanoma correlate with a generally impaired T-cell responsiveness and are restored after dendritic cell-based vaccination.晚期黑色素瘤患者调节性 T 细胞频率增加与普遍受损的 T 细胞反应相关，并在基于树突状细胞的疫苗接种后得到恢复。
Exp Dermatol. 2010 Aug;19(8):e213-21. doi: 10.1111/j.1600-0625.2009.01055.x.
10
Phase I study of autologous dendritic cell tumor vaccine in patients with non-small cell lung cancer.自体树突状细胞瘤苗治疗非小细胞肺癌的Ⅰ期临床研究。
Lung Cancer. 2010 Nov;70(2):188-94. doi: 10.1016/j.lungcan.2010.02.006. Epub 2010 Mar 12.