• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of neuroinflammation >Dendritic cell CNS recruitment correlates with disease severity in EAE via CCL2 chemotaxis at the blood–brain barrier through paracellular transmigration and ERK activation
【24h】

Dendritic cell CNS recruitment correlates with disease severity in EAE via CCL2 chemotaxis at the blood–brain barrier through paracellular transmigration and ERK activation

机译：树突状细胞中枢神经系统募集与EAE中疾病的严重程度有关，通过细胞旁迁移和ERK激活通过血脑屏障处的CCL2趋化作用

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Background Transmigration of circulating dendritic cells (DCs) into the central nervous system (CNS) across the blood–brain barrier (BBB) has not thus far been investigated. An increase in immune cell infiltration across the BBB, uncontrolled activation and antigen presentation are influenced by chemokines. Chemokine ligand 2 (CCL2) is a potent chemoattractant known to be secreted by the BBB but has not been implicated in the recruitment of DCs specifically at the BBB. Methods Experimental autoimmune encephalomyelitis (EAE) was induced in C57BL/6 mice by injection of MOG35–55 peptide and pertussis toxin intraperitoneally. Animals with increasing degree of EAE score were sacrificed and subjected to near-infrared and fluorescence imaging analysis to detect and localize the accumulation of CD11c+-labeled DCs with respect to CCL2 expression. To further characterize the direct effect of CCL2 in DC trafficking at the BBB, we utilized an in vitro BBB model consisting of human brain microvascular endothelial cells to compare migratory patterns of monocyte-derived dendritic cells, CD4+ and CD8+ T cells. Further, this model was used to image transmigration using fluorescence microcopy and to assess specific molecular signaling pathways involved in transmigration. Results Near-infrared imaging of DC transmigration correlated with the severity of inflammation during EAE. Ex vivo histology confirmed the presence of CCL2 in EAE lesions, with DCs emerging from perivascular spaces. DCs exhibited more efficient transmigration than T cells in BBB model studies. These observations correlated with transwell imaging, which indicated a paracellular versus transcellular pattern of migration by DCs and T cells. Moreover, at the molecular level, CCL2 seems to facilitate DC transmigration in an ERK1/2-dependent manner. Conclusion CNS recruitment of DCs correlates with disease severity in EAE via CCL2 chemotaxis and paracellular transmigration across the BBB, which is facilitated by ERK activation. Overall, these comprehensive studies provide a state-of-the-art view of DCs within the CNS, elucidate their path across the BBB, and highlight potential mechanisms involved in CCL2-mediated DC trafficking.
机译：背景技术迄今为止，尚未研究过循环树突状细胞（DCs）跨血脑屏障（BBB）向中枢神经系统（CNS）的迁移。趋化因子影响整个BBB的免疫细胞浸润的增加，不受控制的激活和抗原呈递。趋化因子配体2（CCL2）是一种有效的化学引诱剂，已知由BBB分泌，但并未涉及DC在BBB中的募集。方法通过腹腔注射MOG35–55肽和百日咳毒素，在C57BL / 6小鼠中诱发实验性自身免疫性脑脊髓炎（EAE）。处死具有增加的EAE得分的动物，并进行近红外和荧光成像分析，以检测和定位相对于CCL2表达的CD11c +标记的DC的积累。为了进一步表征CCL2在BBB的DC转运中的直接作用，我们利用了由人脑微血管内皮细胞组成的体外BBB模型来比较单核细胞衍生的树突状细胞，CD4 +和CD8 + T细胞的迁移模式。此外，该模型用于使用荧光显微镜对转移进行成像，并评估涉及转移的特定分子信号传导途径。结果DC迁移的近红外成像与EAE期间炎症的严重程度有关。离体组织学证实在EAE病变中存在CCL2，DC从血管周围间隙中出现。在BBB模型研究中，DC表现出比T细胞更有效的转运。这些观察结果与transwell成像相关，这表明DC和T细胞迁移的细胞旁和跨细胞模式。此外，在分子水平上，CCL2似乎以ERK1 / 2依赖性方式促进DC迁移。结论中枢神经系统中枢神经系统的募集与EAE的疾病严重程度有关，其通过CCL2趋化性和跨BBB的细胞旁迁移而受到ERK激活的促进。总体而言，这些全面的研究提供了CNS中DC的最新视图，阐明了它们穿越BBB的路径，并强调了CCL2介导的DC交易涉及的潜在机制。

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