...
  • 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 >Cross-regulation of TNF and IFN-α in autoimmune diseases
【24h】

Cross-regulation of TNF and IFN-α in autoimmune diseases

机译：自身免疫性疾病中TNF和IFN-α的交叉调节

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

Cytokines, most particularly TNF and type Ⅰ IFN (IFN-αβ), have been long considered essential elements in the development of auto-immunity. Identification of TNF in the pathogenesis of rheumatoid arthritis and TNF antagonist therapy represent successes of immunology. IFN-αβ plays a major role in systemic lupus erythematosus (SLE), a prototype autoimmune disease characterized by a break of tolerance to nuclear components. Here, we show that TNF regulates IFN-α production in vitro at two levels. First, it inhibits the generation of plasmacytoid dendritic cells (pDCs), a major producer of IFN-αβ, from CD34~+ hematopoietic progenitors. Second, it inhibits IFN-α release by immature pDCs exposed to influenza virus. Neutralization of endogenous TNF sustains IFN-α secretion by pDCs. These findings are clinically relevant, as five of five patients with systemic juvenile arthritis treated with TNF antagonists display overexpression of IFN-α-regulated genes in their blood leukocytes. These results, therefore, might provide a mechanistic explanation for the development of anti-dsDNA antibodies and lupus-like syndrome in patients undergoing anti-TNF therapy.
机译：长期以来，人们一直认为细胞因子，特别是TNF和Ⅰ型IFN（IFN-αβ）是发展自身免疫的基本要素。在类风湿性关节炎的发病机理中鉴定TNF和TNF拮抗剂治疗代表了免疫学的成功。 IFN-αβ在系统性红斑狼疮（SLE）中起主要作用，系统性红斑狼疮是一种自身免疫性疾病的原型，其特征是对核成分的耐受性下降。在这里，我们显示了TNF在体外以两个水平调节IFN-α的产生。首先，它抑制CD34〜+造血祖细胞产生浆细胞样树突状细胞（pDC），后者是IFN-αβ的主要产生者。其次，它通过暴露于流感病毒的未成熟pDC抑制IFN-α的释放。内源性TNF的中和维持了pDC的IFN-α分泌。这些发现与临床相关，因为接受TNF拮抗剂治疗的五名系统性幼年关节炎患者中有五名在其白血球中过表达IFN-α调节的基因。因此，这些结果可能为接受抗TNF治疗的患者中抗dsDNA抗体和狼疮样综合征的发生发展提供了机械的解释。

著录项

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