Deletion of RBP-J in dendritic cells compromises TLR-mediated DC activation accompanied by abnormal cytoskeleton reorganization
Deletion of RBP-J in dendritic cells compromises TLR-mediated DC activation accompanied by abnormal cytoskeleton reorganization
复制标题
树突状细胞中 RBP-J 的缺失会损害 TLR 介导的 DC 激活，并伴有异常的细胞骨架重组
DOI：
10.1007/s11033-012-2198-3
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发表时间：
2013-02-01
影响因子：
2.8
通讯作者：
Han, Hua
中科院分区：
文献类型：
--
作者：
Chen, Yun-Ru;Feng, Fan;Han, Hua
树突状细胞(DC)是一种专职的抗原提呈细胞，可以激活和调节免疫反应，但DC激活的机制尚未完全清楚。在这项研究中，我们利用小鼠骨髓来源的DC来研究Notch信号在DC激活中的作用。树突状细胞Toll样受体(TLRs)的激活导致Notch配体表达上调。Notch信号的缺失导致DC激活T细胞的能力下降。RBP-J是介导所有Notch受体的规范信号的关键转录因子。此外，RBP-J缺乏改变了T细胞激活的极化，表现为内毒素或Poly(I：C)刺激后干扰素-γ表达下调，IL-4和IL-10表达上调。此外，我们还发现RBP-J−/−树突状细胞在TLR触发后降低了细胞内钙离子浓度。免疫荧光染色显示RBP-J缺陷树突状细胞与T细胞接触时细胞骨架重组减弱。综上所述，我们的结果表明，规范的Notch信号促进了细胞骨架的重组和TLR介导的DC激活。
Dendritic cells (DCs) are professional antigen presenting cells that activate and modulate immune responses, but the mechanisms underlying DC activation have not been fully understood. In this study, we investigated the role of Notch signaling in DC activation by using murine bone marrow-derived DCs. Triggering of Toll-like receptors (TLRs) of DCs led to upregulated expression of Notch ligands. Disruption of Notch signaling by the deletion of RBP-J, the critical transcription factor mediating the canonical signaling from all Notch receptors, resulted in a reduced capacity of DCs in activating T cells. Moreover, RBP-J deficiency altered the polarization of T cell activation, as manifested by downregulated interferon-γ and upregulated interleukin-4 and -10 expressions after LPS or Poly(I:C) stimulation. Furthermore, we found that RBP-J−/−DCs had reduced intracellular calcium after TLR-triggering. Immunofluorescent staining showed that RBP-J deficient DCs exhibited attenuated cytoskeleton reorganization when contacting T cells. In summary, our results suggested that the canonical Notch signaling promotes the cytoskeleton reorganization and the TLR-mediated DC activation.