ABSTRACT We recently demonstrated that the polysaccharide component of the Korean medicinal herb Angelica gigas (immuno-stimulatory fraction of A. gigas; ISAg) induces anticancer effects in mice by activating natural killer (NK) and natural killer T (NKT) cells. However, it is unclear whether the use of ISAg in vivo can affect the differentiation of conventional T cells. Here, we investigated the effects of ISAg on the activation of conventional CD4+ and CD8+ T cells. We found that the administration of ISAg induced the polarization of CD4+ T cells toward the acquisition of the Th1 phenotype in vivo. Additionally, in mice treated with ISAg, CD8+ T cells produced more IFNγ than in control mice treated with PBS. Moreover, treatment with ISAg activated CD4+ and CD8+ T cells as well as NK and NKT cells, resulting in the secretion of Th1-type cytokines in a toll-like receptor 4 (TLR4)-dependent manner, implying that TLR4 is critical for an optimal Th1 response. Interestingly, ISAg treatment increased the number of Foxp3+ Treg cells, but not of Th2 cells, compared to control mice treated with PBS, indicating that ISAg possesses an immunomodulatory capacity that can control adaptive immune responses. Taken together, our results indicate that ISAg possesses a Th1-enhancing activity that could be used to treat Th2-mediated allergic immune diseases such as atopic dermatitis.

中文翻译：

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ISAg 治疗对体内常规 T 细胞极化的 TLR4 依赖性影响

摘要我们最近证明了韩国药材当归（A. gigas 的免疫刺激部分；ISAg）的多糖成分通过激活自然杀伤 (NK) 和自然杀伤 T (NKT) 细胞在小鼠中诱导抗癌作用。然而，目前尚不清楚体内 ISAg 的使用是否会影响常规 T 细胞的分化。在这里，我们研究了 ISAg 对常规 CD4+ 和 CD8+ T 细胞活化的影响。我们发现 ISAg 的给药诱导 CD4+ T 细胞极化，在体内获得 Th1 表型。此外，在用 ISAg 处理的小鼠中，CD8+ T 细胞比用 PBS 处理的对照小鼠产生更多的 IFNγ。此外，用 ISAg 处理激活 CD4+ 和 CD8+ T 细胞以及 NK 和 NKT 细胞，导致以 toll 样受体 4 (TLR4) 依赖性方式分泌 Th1 型细胞因子，这意味着 TLR4 对最佳 Th1 反应至关重要。有趣的是，与用 PBS 处理的对照小鼠相比，ISAg 处理增加了 Foxp3+ Treg 细胞的数量，但没有增加 Th2 细胞的数量，表明 ISAg 具有可以控制适应性免疫反应的免疫调节能力。总之，我们的结果表明 ISAg 具有 Th1 增强活性，可用于治疗 Th2 介导的过敏性免疫疾病，如特应性皮炎。表明 ISAg 具有免疫调节能力，可以控制适应性免疫反应。总之，我们的结果表明 ISAg 具有 Th1 增强活性，可用于治疗 Th2 介导的过敏性免疫疾病，如特应性皮炎。表明 ISAg 具有免疫调节能力，可以控制适应性免疫反应。总之，我们的结果表明 ISAg 具有 Th1 增强活性，可用于治疗 Th2 介导的过敏性免疫疾病，如特应性皮炎。