Eomesodermin (Eomes), a transcription factor, could suppress the Th17 cell differentiation and proliferation through directly binding to the promoter zone of the Rorc and Il17a gene, meanwhile the expression of Eomes is suppressed when c-Jun directly binds to its promoter zone. Ginkgolide K (1,10-dihydroxy-3,14-didehydroginkgolide, GK) is a diterpene lactone isolated from the leaves of Ginkgo biloba. A previous study indicated that GK could decrease the level of phospho JNK (c-Jun N-terminal kinase). Here, we reported the therapeutic potential of Ginkgolide K (GK) treatment to ameliorate experimental autoimmune encephalomyelitis (EAE) disease progression./nMethods: EAE was induced in both wildtype and CD4-Eomes conditional knockout mice. GK was injected intraperitoneally. Disease severity, inflammation, and tissue damage were assessed by clinical evaluation, flow cytometry of mononuclear cells (MNCs), and histopathological evaluation. Dual-luciferase reporter assays were performed to measure Eomes transcription activity in vitro. The potency of GK (IC₅₀) was determined using JNK1 Kinase Enzyme System./nResults: We revealed that GK could ameliorate EAE disease progression by the inhibition of the Th17 cells. Further mechanism studies demonstrated that the level of phospho JNK was decreased and the level of Eomes in CD4⁺T cells was dramatically increased. This therapeutic effect of GK was almost completely interrupted in CD4-Eomes conditional knockout mice./nConclusions: These results provided the therapeutic potential of GK treatment in EAE, and further suggested that Eomes expression in CD4⁺T cells might be essential in this process.

中文翻译：

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CD4+T 细胞中的 Eomesodermin 对于银杏内酯 K 改善实验性自身免疫性脑脊髓炎疾病进展至关重要


Eomesodermin (Eomes)是一种转录因子，通过直接结合Rorc和Il17a基因的启动子区，可以抑制Th17细胞的分化和增殖，同时当c-Jun直接与其启动子区结合时， Eomes的表达受到抑制。银杏内酯 K (1,10-二羟基-3,14-二脱氢银杏内酯, GK) 是从银杏叶中分离出来的二萜内酯。先前的研究表明，GK 可以降低磷酸 JNK（c-Jun N 末端激酶）的水平。在这里，我们报告了银杏内酯 K (GK) 治疗改善实验性自身免疫性脑脊髓炎 (EAE) 疾病进展的治疗潜力。/n 方法：在野生型和 CD4- Eomes条件敲除小鼠中诱导 EAE。 GK腹腔注射。通过临床评估、单核细胞（MNC）流式细胞术和组织病理学评估来评估疾病严重程度、炎症和组织损伤。进行双荧光素酶报告基因测定以测量 Eomes 体外转录活性。 GK 的效力 (IC ₅₀ ) 使用 JNK1 激酶酶系统测定。/n结果：我们发现 GK 可以通过抑制 Th17 细胞来改善 EAE 疾病进展。进一步的机制研究表明，CD4 ⁺ T细胞中磷酸化JNK水平降低，Eomes水平显着升高。 GK 的这种治疗作用在 CD4- Eomes条件敲除小鼠中几乎完全中断。/n结论：这些结果提供了 GK 治疗 EAE 的治疗潜力，并进一步表明 CD4 ⁺ T 细胞中的 Eomes 表达可能在此过程中至关重要。