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首页> 外文期刊>Cellular immunology >Uncarinic acid C plus IFN-gamma generates monocyte-derived dendritic cells and induces a potent Th1 polarization with capacity to migrate.
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Uncarinic acid C plus IFN-gamma generates monocyte-derived dendritic cells and induces a potent Th1 polarization with capacity to migrate.

机译：非carcaricic酸C加IFN-γ产生单核细胞衍生的树突状细胞，并诱导强大的Th1极化并具有迁移能力。

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Uncarinic acid C (URC) is triterpene isolated from Uncaria rhynchophylla and modulates human DC function in a fashion that favors Th1 cell polarization depending on TLR4 signaling. The induction of dendritic cells (DC) is critical for the induction of Ag-specific T lymphocyte responses and may be essential for the development of human vaccines relying on T cell immunity. Monocyte-derived DC used as adjuvant cells in cancer immunotherapy and have shown promising results. We studied the effect of interferon's (IFN-alpha and IFN-gamma) and TNF-alpha on phenotypic and functional maturation, and cytokine production of URC-primed DC in vitro. Human monocytes were exposed to either URC alone, or in combination with TNF-alpha, IFN-alpha or IFN-gamma, and thereafter co-cultured with naive T cells. We found that the expression levels of CD1a, CD83 and HLA-DR on URC-primed DC were influenced by IFN-gamma and IFN-gamma augmented the T cell stimulatory capacity in allo MLR to URC-primed DC. Moreover, the production of IL-12p70 by URC-primed DC was enhanced by IFN-gamma. IL-12p70 production by URC-primed DC alone was influenced following treatment with anti-TLR4 mAb, but not DC differentiated with URC plus IFN-gamma. URC plus IFN-gamma-primed DC induced a substantial increase in the secretion of IFN-gamma by T cells, which is dependent on IL-12 secretion. DC maturated with URC plus IFN-gamma had an intermediate migratory capacity towards CCL19 and CCL21. In addition, the expression levels of CCR7 on URC-primed DC were enhanced by IFN-gamma. In contrast, surface molecule up-regulation and function of URC-primed DC were slightly enhanced by TNF-alpha, and IFN-alpha. These results suggest that the enhancement of Th1 cells polarization to URC-primed DC induced by IFN-gamma depends on the activation of IL-12p70 and independent on TLR4. DC differentiated with URC in combination with IFN-gamma might be used on DC-based vaccine for cancer immunotherapy.
机译：非carcaricic acid C（URC）是从钩藤（Uncaria rhynchophylla）分离的三萜，并根据TLR4信号转导有助于Th1细胞极化的方式调节人类DC功能。树突状细胞（DC）的诱导对于诱导Ag特异的T淋巴细胞应答至关重要，对于依赖T细胞免疫的人类疫苗的开发可能至关重要。单核细胞衍生的DC在癌症免疫治疗中用作佐剂细胞，并显示出令人鼓舞的结果。我们研究了干扰素（IFN-α和IFN-γ）和TNF-α对URC引发的DC的表型和功能成熟以及细胞因子产生的影响。将人单核细胞单独暴露于URC，或与TNF-α，IFN-α或IFN-γ联合使用，然后与幼稚T细胞共培养。我们发现，IFN-γ影响了URC启动的DC上CD1a，CD83和HLA-DR的表达水平，而IFN-γ增强了ULR启动的同种异体MLR中的T细胞刺激能力。而且，通过IFN-γ增强了由URC引发的DC产生的IL-12p70。用抗TLR4 mAb处理后，单独由URC引发的DC产生的IL-12p70受到影响，但不受URC加IFN-γ分化的DC的影响。 URC加IFN-γ引发的DC诱导T细胞的IFN-γ分泌大量增加，这取决于IL-12的分泌。用URC和IFN-γ成熟的DC对CCL19和CCL21具有中等的迁移能力。另外，通过IFN-γ增强了在URC引发的DC上CCR7的表达水平。相反，TNF-α和IFN-α略微增强了URC启动的DC的表面分子上调和功能。这些结果表明，IFN-γ诱导的Th1细胞极化增强至URC启动的DC取决于IL-12p70的激活，而与TLR4无关。用URC分化的DC结合IFN-γ可用于基于DC的疫苗进行癌症免疫治疗。

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