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首页> 外文期刊>Clinical and vaccine immunology: CVI >All-trans-Retinoic Acid Imprints Expression of the Gut-Homing Marker α4β7 while Suppressing Lymph Node Homing of Dendritic Cells
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All-trans-Retinoic Acid Imprints Expression of the Gut-Homing Marker α4β7 while Suppressing Lymph Node Homing of Dendritic Cells

机译：全反式维甲酸抑制肠道树突状细胞淋巴结归巢时，肠归巢标记α4β7的表达。

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Tissue-directed trafficking of dendritic cells (DCs) as natural adjuvants and/or direct vaccine carriers is highly attractive for the next generation of vaccines and immunotherapeutics. Since these types of studies would undoubtedly be first conducted using nonhuman primate models, we evaluated the ability of all-trans-retinoic acid (ATRA) to induce gut-homing α4β7 expression on rhesus macaque plasmacytoid and myeloid DCs (pDCs and mDCs, respectively). Induction of α4β7 occurred in both a time-dependent and a dose-dependent manner with up to 8-fold increases for mDCs and 2-fold increases for pDCs compared to medium controls. ATRA treatment was also specific in inducing α4β7 expression, but not expression of another mucosal trafficking receptor, CCR9. Unexpectedly, upregulation of α4β7 was associated with a concomitant downregulation of CD62L, a marker of lymph node homing, indicating an overall shift in the trafficking repertoire. These same phenomena occurred with ATRA treatment of human and chimpanzee DCs, suggesting a conserved mechanism among primates. Collectively, these data serve as a first evaluation for ex vivo modification of primate DC homing patterns that could later be used in reinfusion studies for the purposes of immunotherapeutics or mucosa-directed vaccines.
机译：作为天然佐剂和/或直接疫苗载体的组织定向树突细胞（DCs）的运输对于下一代疫苗和免疫疗法非常有吸引力。由于无疑将首先使用非人类灵长类动物模型进行这些类型的研究，因此我们评估了全反式-视黄酸（ATRA）诱导恒河猴猕猴浆细胞样细胞和髓样DCs上肠归巢α4β7表达的能力。 （分别为pDC和mDC）。与培养基对照相比，α4β7的诱导以时间依赖性和剂量依赖性方式发生，其中mDC最多增加8倍，pDC最多增加2倍。 ATRA治疗也特异性诱导α4β7表达，但不诱导另一种粘膜运输受​​体CCR9的表达。出乎意料的是，α4β7的上调与伴随淋巴结归巢的标志物CD62L的下调相关，表明贩运库中的总体变化。在人类和黑猩猩DC的ATRA处理中也发生了相同的现象，这表明灵长类动物存在保守的机制。总的来说，这些数据是对灵长类DC归巢模式的“体外”修饰的首次评估，该模式随后可用于免疫治疗或粘膜定向疫苗的再输注研究。

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