DEC-205 is a cell surface receptor for CpG oligonucleotides
DEC-205 is a cell surface receptor for CpG oligonucleotides
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DOI：
10.1073/pnas.1208796109
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发表时间：
2012-10-02
影响因子：
11.1
通讯作者：
Caminschi, Irina
中科院分区：
文献类型：
--
作者：
Lahoud, Mireille H.;Ahmet, Fatma;Caminschi, Irina
合成CpG寡核苷酸（ODN）在临床疫苗试验中具有有效的免疫刺激特性。然而，CpG ODN如何被捕获并传递给细胞内受体TLR9一直是难以捉摸的。本研究表明，多种细胞表达的多集素受体DEC-205是CpG ODN的受体。当CpG ODN用作佐剂时，缺乏DEC-205的小鼠树突状细胞（DC）和b细胞成熟受损，无法产生某些细胞因子，如IL-12，并表现出次优的细胞毒性t细胞反应。我们发现DEC-205直接结合B类CpG ODN并增强它们的摄取。DEC-205的CpG-ODN结合功能在小鼠和人之间是保守的，尽管人类DEC-205优先结合特定的B类CpG ODN，该CpG ODN已被选择用于人类临床试验。我们的研究结果确定了B类CpG ODN的一个重要受体，并揭示了DEC-205的独特功能。
Synthetic CpG oligonucleotides (ODN) have potent immunostimulatory properties exploited in clinical vaccine trials. How CpG ODN are captured and delivered to the intracellular receptor TLR9, however, has been elusive. Here we show that DEC-205, a multilectin receptor expressed by a variety of cells, is a receptor for CpG ODN. When CpG ODN are used as an adjuvant, mice deficient in DEC-205 have impaired dendritic cell (DC) and B-cell maturation, are unable to make some cytokines such as IL-12, and display suboptimal cytotoxic T-cell responses. We reveal that DEC-205 directly binds class B CpG ODN and enhances their uptake. The CpG-ODN binding function of DEC-205 is conserved between mouse and man, although human DEC-205 preferentially binds a specific class B CpG ODN that has been selected for human clinical trials. Our findings identify an important receptor for class B CpG ODN and reveal a unique function for DEC-205.