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Exacerbation of Japanese Encephalitis by CD11chi Dendritic Cell Ablation Is Associated with an Imbalance in Regulatory Foxp3+ and IL-17+CD4+ Th17 Cells and in Ly-6Chi and Ly-6Clo Monocytes
Immune Network ( IF 6 ) Pub Date : 2017-01-01 , DOI: 10.4110/in.2017.17.3.192
Jin Young Choi 1 , Jin Hyoung Kim 1 , Ajit Mahadev Patil 1 , Seong Bum Kim 1 , Erdenebelig Uyangaa 1 , Ferdaus Mohd Altaf Hossain 1 , Seong Kug Eo 1, 2
Affiliation  

Japanese encephalitis (JE) is neuroinflammation characterized by uncontrolled infiltration of peripheral leukocytes into the central nervous system (CNS). We previously demonstrated exacerbation of JE following CD11chi dendritic cell (DC) ablation in CD11c-DTR transgenic mice. Moreover, CD11chi DC ablation led to abnormal differentiation of CD11b+Ly-6Chi monocytes and enhanced permeability of the blood-brain barrier (BBB), resulting in promoting the progression of JE. Here, we examined changes in lymphoid and myeloid-derived leukocyte subpopulations associated with pro- and anti-inflammation during JE progression. The analyses of this study focused on regulatory CD4+Foxp3+ regulatory T cells (Tregs), IL-17+CD4+ Th17 cells, and CD11b+Ly-6Chi and Ly-6Clo monocytes. CD11chi DC ablation resulted in the accumulation of IL-17+CD4+ Th17 cells in the CNS, thereby leading to lower ratio of Tregs to Th17 cells. This result was corroborated by the higher expression levels of IL-17 and RORγT in CD4+ T cells from the brains of CD11chi DC-ablated mice. In addition, CD11chi DC-ablated mice showed higher frequency and total number of inflammatory CD11b+Ly-6Chi monocytes, whereas CD11b+Ly-6Clo monocytes were detected with lower frequency and total number in CD11chi DC-ablated mice. Furthermore, CD11chi DC ablation altered the phenotype and function of CD11b+Ly-6Clo monocytes, resulting in lower levels of activation marker and anti-inflammatory cytokine (IL-10 and TGF-β) expression. Collectively, these results indicate that CD11chi DC ablation caused an imbalance in CD4+ Th17/Treg cells and CD11b+Ly-6Chi/Ly-6Clo monocytes in the lymphoid tissue and CNS during JE progression. This imbalanced orchestration of pro- and anti-inflammatory leukocytes following CD11chi DC ablation may contribute to the exacerbation of JE.

中文翻译:

CD11chi 树突状细胞消融导致日本脑炎恶化与调节性 Foxp3+ 和 IL-17+CD4+ Th17 细胞以及 Ly-6Chi 和 Ly-6Clo 单核细胞的失衡有关

日本脑炎 (JE) 是一种神经炎症,其特征是外周白细胞不受控制地浸润到中枢神经系统 (CNS) 中。我们之前证明了 CD11c-DTR 转基因小鼠中 CD11chi 树突状细胞 (DC) 消融后 JE 的恶化。此外,CD11chi DC 消融导致 CD11b+Ly-6Chi 单核细胞的异常分化和血脑屏障 (BBB) 通透性增强,从而促进了乙脑的进展。在这里,我们检查了在乙脑进展过程中与促炎和抗炎相关的淋巴和髓样白细胞亚群的变化。本研究的分析侧重于调节性 CD4+Foxp3+ 调节性 T 细胞 (Tregs)、IL-17+CD4+ Th17 细胞以及 CD11b+Ly-6Chi 和 Ly-6Clo 单核细胞。CD11chi DC 消融导致中枢神经系统中 IL-17+CD4+Th17 细胞的积累,从而导致 Tregs 与 Th17 细胞的比率较低。来自 CD11chi DC 消融小鼠大脑的 CD4+ T 细胞中 IL-17 和 RORγT 的更高表达水平证实了这一结果。此外,CD11chi DC 消融小鼠显示出较高的炎症性 CD11b+Ly-6Chi 单核细胞的频率和总数,而 CD11b+Ly-6Clo 单核细胞在 CD11chi DC 消融的小鼠中以较低的频率和总数检测到。此外,CD11chi DC 消融改变了 CD11b+Ly-6Clo 单核细胞的表型和功能,导致激活标志物和抗炎细胞因子(IL-10 和 TGF-β)表达水平降低。总的来说,这些结果表明,在乙脑进展过程中,CD11chi DC 消融导致淋巴组织和 CNS 中 CD4+ Th17/Treg 细胞和 CD11b+Ly-6Chi/Ly-6Clo 单核细胞的不平衡。
更新日期:2017-01-01
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