...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Avidity of CD1d-ligand-receptor ternary complex contributes to T-helper 1 (Th1) polarization and anticancer efficacy
【24h】

Avidity of CD1d-ligand-receptor ternary complex contributes to T-helper 1 (Th1) polarization and anticancer efficacy

机译：CD1d-配体-受体三元复合物的亲和力有助于T-helper 1（Th1）极化和抗癌功效

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Invariant natural killer T cell (NKT) cells (iNKT cells) produce both T-helper 1 (Th1) and T-helper 2 cytokines in response to α-Galacto-sylceramide (α-GalCer) stimulation and are thought to be the important effectors in the regulation of both innate and adaptive immunity involved in autoimmune disorders, microbial infections, and cancers. However, the anticancer effects of a-GalCer were limited in early clinical trial. In this study, several analogs of a-GalCer, containing phenyl groups in the lipid tails were found to stimulate murine and human iNKT cells to secrete Th1-skewed cytokines and exhibit greater anticancer efficacy in mice than a-GalCer. We explored the possibility of different Vβ usages of murine Vα14 iNKT or human Vα24 /NKT cells, accounting for differential cytokine responses. However, T-cell receptor Vβ analysis revealed no significant differences in Vβ usages by α-GalCer and these phenyl glyco-lipid analogs. On the other hand, these phenyl glycolipids showed greater binding avidity and stability for iNKT T-cell receptor when complexed with CD1d. These findings suggest that CD1d-phenyl glycolipid complexes may interact with the same population of iNKT cells but with higher avidity and stability to drive Thi polarization. Thus, this study provides a key to the rational design of Th1 biased CD1d reactive glycolipids in the future.
机译：不变的自然杀伤性T细胞（NKT）细胞（iNKT细胞）响应α-半乳糖苷神经酰胺（α-GalCer）刺激而产生T辅助1（Th1）和T辅助2细胞因子，被认为是重要的效应子涉及自身免疫性疾病，微生物感染和癌症的先天和适应性免疫的调节。但是，a-GalCer的抗癌作用在早期临床试验中受到限制。在这项研究中，发现在脂尾中含有苯基的a-GalCer的几种类似物可刺激鼠和人iNKT细胞分泌Th1偏斜的细胞因子，并在小鼠中显示出比a-GalCer更大的抗癌功效。我们探讨了鼠Vα14iNKT或人Vα24/ NKT细胞使用不同Vβ的可能性，从而解释了不同的细胞因子反应。但是，T细胞受体Vβ分析显示，α-GalCer和这些苯基糖脂类似物在Vβ用法方面无显着差异。另一方面，这些苯基糖脂与CD1d复合后，对iNKT T细胞受体显示出更大的结合亲和力和稳定性。这些发现表明，CD1d-苯基糖脂复合物可能与相同的iNKT细胞群体相互作用，但具有更高的亲和力和稳定性来驱动Thi极化。因此，本研究为将来合理设计Th1偏置CD1d反应性糖脂提供了关键。

著录项

  • 来源
  • 作者

    Tai-Na Wu; Kun-Hsien Lin; Ya-Jen Chang; Jing-Rong Huang; Jing-Yan Cheng; Alice L. Yu; Chi-Huey Wong;

  • 作者单位

    Genomics Research Center, Academia Sinica, Taipei 115, Taiwan,Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan;

    Genomics Research Center, Academia Sinica, Taipei 115, Taiwan,Department of Chemistry, National Taiwan University, Taipei 106, Taiwan;

    Genomics Research Center, Academia Sinica, Taipei 115, Taiwan;

    Genomics Research Center, Academia Sinica, Taipei 115, Taiwan,Institute and Department of Microbiology and Immunology,National Yang-Ming University, Taipei 112, Taiwan;

    Genomics Research Center, Academia Sinica, Taipei 115, Taiwan,Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan;

    Genomics Research Center, Academia Sinica, Taipei 115, Taiwan;

    Genomics Research Center, Academia Sinica, Taipei 115, Taiwan;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号