Abstract：
BACKGROUND: Guillain-Barré syndrome (GBS) is an auto-inflammatory peripheral nerve disease. Dendritic cell-mediated T cell polarization is of pivotal importance in demyelinating lesions of peripheral nerves and nerve roots. However, the regulatory function of VX-509 (Decernotinib)-modified tolerogenic dendritic cells (VX-509-tolDCs) during immune remodeling following GBS remains unclear. Here, we used experimental autoimmune neuritis (EAN) as a model to investigate these aspects of GBS.
METHODS: DCs were treated with varying concentrations of VX-509 (0.25, 1, and 4 μM) or served as a control using 10-8 M 1,25-(OH)2D3. Flow cytometry was employed to assess the apoptosis, phenotype, and capacity to induce T cell responses of the treated DCs. In the in vivo experiments, EAN mice received administration of VX-509-tolDCs or 1,25-(OH)2D3-tolDCs via the tail vein at a dose of 1x106 cells/mouse on days 5, 9, 13, and 17.
RESULTS: VX-509 inhibited the maturation of DCs and promoted the development of tolDCs. The function of antigen-specific CD4 + T cells ex vivo was influenced by VX-509-tolDCs. Furthermore, the adoptive transfer of VX-509-tolDCs effectively alleviated inflammatory demyelinating lesions in EAN by promoting Th17/Treg (T helper 17 and regulatory T cells) rebalance.
CONCLUSIONS: The adoptive transfer of VX-509-tolDCs alleviated inflammatory demyelinating lesions in a mouse model of GBS, known as the EAN mouse, by partially restoring the balance between Treg and Th17 cells.
METHODS: DCs were treated with varying concentrations of VX-509 (0.25, 1, and 4 μM) or served as a control using 10-8 M 1,25-(OH)2D3. Flow cytometry was employed to assess the apoptosis, phenotype, and capacity to induce T cell responses of the treated DCs. In the in vivo experiments, EAN mice received administration of VX-509-tolDCs or 1,25-(OH)2D3-tolDCs via the tail vein at a dose of 1x106 cells/mouse on days 5, 9, 13, and 17.
RESULTS: VX-509 inhibited the maturation of DCs and promoted the development of tolDCs. The function of antigen-specific CD4 + T cells ex vivo was influenced by VX-509-tolDCs. Furthermore, the adoptive transfer of VX-509-tolDCs effectively alleviated inflammatory demyelinating lesions in EAN by promoting Th17/Treg (T helper 17 and regulatory T cells) rebalance.
CONCLUSIONS: The adoptive transfer of VX-509-tolDCs alleviated inflammatory demyelinating lesions in a mouse model of GBS, known as the EAN mouse, by partially restoring the balance between Treg and Th17 cells.
摘要：
背景：格林-巴利综合征（GBS）是一种自身炎症性周围神经疾病。树突状细胞介导的T细胞极化在周围神经和神经根的脱髓鞘病变中至关重要。然而,VX-509(Decernotinib)修饰的致耐受性树突状细胞(VX-509-tolDCs)在GBS后免疫重塑过程中的调节功能尚不清楚.这里,我们使用实验性自身免疫性神经炎(EAN)作为模型来研究GBS的这些方面.
方法:用不同浓度的VX-509(0.25、1和4μM)处理DC或使用10-8M1,25-(OH)2D3作为对照。流式细胞术用于评估细胞凋亡，表型,以及诱导经处理的DC的T细胞应答的能力。在体内实验中，在第5、9、13和17天，EAN小鼠通过尾静脉以1×106个细胞/小鼠的剂量接受VX-509-tolDC或1,25-（OH）2D3-tolDC。
结果：VX-509抑制DCs的成熟，促进tolDCs的发育。离体抗原特异性CD4+T细胞的功能受VX-509-tolDC的影响。此外，VX-509-tolDCs的过继转移通过促进Th17/Treg(辅助性T细胞17和调节性T细胞)再平衡有效缓解EAN中的炎性脱髓鞘病变。
结论：VX-509-tolDCs的过继转移减轻了GBS小鼠模型的炎性脱髓鞘病变，被称为EAN鼠标，通过部分恢复Treg和Th17细胞之间的平衡。
方法:用不同浓度的VX-509(0.25、1和4μM)处理DC或使用10-8M1,25-(OH)2D3作为对照。流式细胞术用于评估细胞凋亡，表型,以及诱导经处理的DC的T细胞应答的能力。在体内实验中，在第5、9、13和17天，EAN小鼠通过尾静脉以1×106个细胞/小鼠的剂量接受VX-509-tolDC或1,25-（OH）2D3-tolDC。
结果：VX-509抑制DCs的成熟，促进tolDCs的发育。离体抗原特异性CD4+T细胞的功能受VX-509-tolDC的影响。此外，VX-509-tolDCs的过继转移通过促进Th17/Treg(辅助性T细胞17和调节性T细胞)再平衡有效缓解EAN中的炎性脱髓鞘病变。
结论：VX-509-tolDCs的过继转移减轻了GBS小鼠模型的炎性脱髓鞘病变，被称为EAN鼠标，通过部分恢复Treg和Th17细胞之间的平衡。
