• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Neuroimmunology: Official Bulletin of the Research Committee on Neuroimmunology of the World Federation of Neurology >Beta7 integrins contribute to demyelinating disease of the central nervous system.
【24h】

Beta7 integrins contribute to demyelinating disease of the central nervous system.

机译：Beta7整合素有助于中枢神经系统脱髓鞘疾病。

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

A role for alpha4 integrins in different forms of the multiple sclerosis-like disease experimental autoimmune encephalomyelitis (EAE) has been demonstrated, but the individual contributions of alpha4beta1, alpha4beta7, and the related alphaEbeta7 integrin have not been determined. The P7 integrins alpha4beta7 and alphaEbeta7 play a central role in chronic inflammation, mediating the trafficking, entry, and/or adhesion of lymphocytes in the inflamed pancreas and gut, and their ligands MAdCAM-1, VCAM-1 and E-cadherin are expressed on brain endothelial cells and/or on microvessels in the inflamed central nervous system. Here, we show that an antibody directed against the beta7 subunit greatly attenuates a non-remitting form of EAE, induced by adoptive transfer of myelin oligodendrocyte peptide (MOG35-55)-stimulated T cells. Combinational treatment with both anti-beta7 and alpha4 integrin subunit antibodies led to more rapid and complete remission than that obtained with anti-alpha4 antibody alone, potentially implicating a role for alphaEbeta7 in disease progression. Remission correlated with the down-regulation of the vascular addressins VCAM-1. MAdCAM-1, and ICAM-1 on cerebral blood vessels. Attenuated forms of disease were induced by adoptive transfer of either wild-type encephalitogenic T cells to beta7-deficient gene knockout mice, or of beta7-/-encephalitogenic T cells to wild-type recipients. The former finding indicates that beta7 + ve recruited cells contribute to disease progression. Thus alpha4beta1, alpha4beta7, and alphaEbeta7 integrins may all play a contributory role in the progression of chronic forms of demyelinating disease, and together with their ligands could represent potential targets for improved treatment of some forms of multiple sclerosis.
机译：已经证明了alpha4整联蛋白在多种形式的多发性硬化症样疾病实验性自身免疫性脑脊髓炎（EAE）中的作用，但尚未确定alpha4beta1，alpha4beta7和相关的alphaEbeta7整联蛋白的单独作用。 P7整合素alpha4beta7和alphaEbeta7在慢性炎症中起关键作用，介导发炎的胰腺和肠道中淋巴细胞的运输，进入和/或粘附，并且它们的配体MAdCAM-1，VCAM-1和E-钙粘着蛋白在大脑中的内皮细胞和/或发炎的中枢神经系统中的微血管。在这里，我们显示了针对beta7亚基的抗体极大地减弱了由髓磷脂少突胶质细胞肽（MOG35-55）刺激的T细胞的过继转移诱导的EAE的一种非发光形式。抗β7和α4整联蛋白亚基抗体的联合治疗比单独使用抗α4抗体获得的治疗更快，更彻底的缓解，这可能暗示了αEbeta7在疾病进展中的作用。缓解与血管地址蛋白VCAM-1的下调有关。脑血管上的MAdCAM-1和ICAM-1。通过将野生型致脑病T细胞过继转移至beta7缺陷型基因敲除小鼠，或将beta7 //致脑病T细胞过继转移至野生型受体来诱导疾病的减轻。前一个发现表明，beta7 + ve募集的细胞有助于疾病的进展。因此，alpha4beta1，alpha4beta7和alphaEbeta7整联蛋白都可能在慢性脱髓鞘疾病的慢性发展过程中发挥重要作用，并且它们的配体一起可能代表改善某些形式的多发性硬化症的潜在治疗靶标。

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