Objective: Cordycepin has been shown to exhibit multiple pharmacological activities, such as antitumor, antifungi, antivirus, and immune-regulation activities, and is involved in the regulation of T cells. However, cordycepin that affects T cell activity is still not clear, and the molecular mechanism of cordycepin in regulation of TCR signaling has not yet been elucidated. In this study, the potential effect of cordycepin on T cells was observed in CFA-induced inflammation mice model, and the function of cordycepin in regulating TCR signaling cascade was investigated.Methods: A CFA-induced inflammation mice model was established for observing the effect of cordycepin on the thymus and spleen swellings, and T cell infiltration in paw tissue was detected by immunohistochemistry. The protein expression or phosphorilation was detected by western blotting, and the NFAT1 nuclear translocation was determined by fluorescence imaging. The cell proliferation, apoptosis, and IL-2 production were analyzed by CCK-8 method, flow cytometry, and ELISA.Results: In the mice model, the thymus and spleen swellings were suppressed and the T cell infiltration in paw tissue was inhibited by cordycepin at a concentration of 10 mg/kg. Although the expressions of ZAP70 and PLCγ1 were not significantly changed in the human T cell line Jurkat with cordycepin pretreatment, the CD3-antibody-induced phosphorylations of ZAP70 and PLCγ1 were markedly blocked. The protein level of p85 decreased when Jurkat cells were pretreated with cordycepin, and cordycepin blocked TCR downstream molecule Erk phosphorylation and NFAT1 nuclear translocation. Further investigation revealed that cordycepin inhibited T cell proliferation, reduced IL-2 production, and induced T cell apoptosis. Conclusions: These findings suggest that cordycepin regulates TCR signaling to inhibit excessive T cell activation in inflammation. Thus, cordycepin may be a potential therapeutic application in inflammation-associated diseases.

中文翻译：

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虫草素通过抑制CFA诱导的炎症小鼠模型中的TCR信号级联反应，对T细胞具有抑制作用。

目的：虫草素已显示出多种药理活性，例如抗肿瘤，抗真菌，抗病毒和免疫调节活性，并参与了T细胞的调节。但是，尚不清楚影响T细胞活性的虫草素，并且尚不清楚虫草素在TCR信号传导调节中的分子机制。本研究在CFA诱导的炎症小鼠模型中观察了虫草素对T细胞的潜在作用，并研究了虫草素在调节TCR信号转导中的作用。方法：建立CFA诱导的炎症小鼠模型，观察其作用。免疫组织化学法检测虫草素对胸腺和脾肿胀的影响，并检测爪组织中的T细胞浸润。通过蛋白质印迹检测蛋白质表达或磷酸化，并通过荧光成像确定NFAT1核易位。结果：在小鼠模型中，抑制了小鼠胸腺和脾肿胀，并抑制了爪状细胞的T细胞浸润，从而通过CCK-8法，流式细胞仪和ELISA分析了细胞的增殖，凋亡和IL-2的产生。虫草素的浓度为10 mg / kg。尽管在用虫草素预处理的人T细胞系Jurkat中ZAP70和PLCγ1的表达没有明显改变，但CD3抗体诱导的ZAP70和PLCγ1的磷酸化被显着阻断。当用虫草素预处理Jurkat细胞时，p85的蛋白水平降低，并且虫草素阻断了TCR下游分子Erk磷酸化和NFAT1核易位。进一步的研究表明，虫草素抑制T细胞增殖，减少IL-2产生并诱导T细胞凋亡。结论：这些发现表明虫草素调节TCR信号传导以抑制炎症中过度的T细胞活化。因此，虫草素可能是炎症相关疾病的潜在治疗应用。