...
  • 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 >Pancreatic islet expression of chemokine CCL2 suppresses autoimmune diabetes via tolerogenic CD11c~+ CD11b~+ dendritic cells
【24h】

Pancreatic islet expression of chemokine CCL2 suppresses autoimmune diabetes via tolerogenic CD11c~+ CD11b~+ dendritic cells

机译：趋化因子CCL2的胰岛表达通过耐受性CD11c〜+ CD11b〜+树突状细胞抑制自身免疫性糖尿病

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

Development of type 1 diabetes in the nonobese diabetic (NOD) mouse is preceded by an immune cell infiltrate in the pancreatic islets. The exact role of the attracted cells is still poorly understood. Chemokine CCL2/MCP-1 is known to attract CCR2~+ monocytes and dendritic cells (DCs). We have previously shown that transgenic expression of CCL2 in pancreatic islets via the rat insulin promoter induces nondestructive insulitis on a nonautoimmune background. We report here an unexpected reduction of diabetes development on the NOD background despite an increased islet cell infiltrate with markedly increased numbers of CD11c~+ CD11b~+ DCs. These DCs exhibited a hypoactive phenotype with low CD40, MHC II, CD80/CD86 expression, and reduced TNF-α but elevated IL-10 secretions. They failed to induce proliferation of diabetogenic CD4~+ T cells in vitro. Pancreatic lymph node CD4~+ T cells were down-regulated ex vivo and expressed the anergy marker Grail. By using an in vivo transfer system, we show that CD11c~+ CD11b~+ DCs from rat insulin promoter-CCL2 transgenic NOD mice were the most potent cells suppressing diabetes development. These findings support an unexpected beneficial role for CCL2 in type 1 diabetes with implications for current strategies interfering with the CCL2/CCR2 axis in humans, and for dendritic cell biology in autoimmunity.
机译：非肥胖糖尿病（NOD）小鼠中1型糖尿病的发生是由胰岛中的免疫细胞浸润引起的。吸引细胞的确切作用仍然知之甚少。已知趋化因子CCL2 / MCP-1会吸引CCR2〜+单核细胞和树突状细胞（DC）。先前我们已经表明，通过大鼠胰岛素启动子在胰岛中CCL2的转基因表达在非自身免疫背景下诱导了非破坏性胰岛炎。尽管胰岛细胞浸润增加，CD11c〜+ CD11b〜+ DC数量明显增加，但我们在这里报道了NOD背景下糖尿病发展的意外减少。这些DC表现出具有低CD40，MHC II，CD80 / CD86表达的低活性表型，并且TNF-α降低但IL-10分泌升高。他们未能在体外诱导致糖尿病的CD4〜+ T细胞增殖。胰腺淋巴结CD4〜+ T细胞离体表达下调，并表达无反应标记物Grail。通过使用体内转移系统，我们显示来自大鼠胰岛素启动子-CCL2转基因NOD小鼠的CD11c〜+ CD11b〜+ DC是抑制糖尿病发展的最有效细胞。这些发现支持了CCL2在1型糖尿病中的出乎意料的有益作用，暗示了目前对人类CCL2 / CCR2轴产生干扰的策略以及对自身免疫中树突状细胞生物学的影响。

著录项

  • 来源
  • 作者

    Martin A. Kriegel; Chozhavendan Rathinam; Richard A. Flavell;

  • 作者单位

    Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520,Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115;

    Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520,Department of Genetics and Development, Columbia University, New York, NY 10032;

    Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520,Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520;

  • 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

    monocyte chemotactic protein-1; immune tolerance; BDC2.5; myeloid DC; B-7;

    机译：单核细胞趋化蛋白-1;免疫耐受BDC2.5;髓样DC;B-7;

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