Altered expression and endocytic function of CD205 in human dendritic cells, and detection of a CD205-DCL-1 fusion protein upon dendritic cell maturation
Altered expression and endocytic function of CD205 in human dendritic cells, and detection of a CD205-DCL-1 fusion protein upon dendritic cell maturation
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DOI：
10.1111/j.1365-2567.2006.02512.x
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发表时间：
2007-03-01
期刊：
影响因子：
6.4
通讯作者：
Ritter, Mary A.
中科院分区：
文献类型：
--
作者：
Butler, Matt;Morel, Anne-Sophie;Ritter, Mary A.
CD 205（DEC-205）是C型凝集素的巨噬细胞甘露糖受体家族的成员。已知这些分子介导多种生物学功能，包括配体的捕获和内化，用于随后的树突细胞加工和呈递。虽然其配体有待鉴定，但CD 205的内吞特性使其成为希望设计疫苗和靶向免疫疗法的人的理想靶标。我们提出了一个详细的分析CD 205的表达，分布和内吞作用的人单核细胞来源的树突状细胞经历脂多糖诱导成熟。与巨噬细胞甘露糖受体家族的其他成员不同，CD 205在树突状细胞成熟后上调。这种增加是从头合成以及分子从内吞隔室重新分布到细胞表面的结果。此外，CD 205的内吞能力被废除，并且在成熟DC中检测到少量最近鉴定的CD 205-DCL-1融合蛋白。我们的研究结果表明，CD 205具有两种不同的功能-一种是作为未成熟树突状细胞上的内吞受体，另一种是作为成熟树突状细胞上的非内吞分子-并进一步突出了其作为疫苗和免疫疗法开发的免疫调节靶点的潜力。
CD205 (DEC-205) is a member of the macrophage mannose receptor family of C-type lectins. These molecules are known to mediate a wide variety of biological functions including the capture and internalization of ligands for subsequent processing and presentation by dendritic cells. Although its ligands await identification, the endocytic properties of CD205 make it an ideal target for those wishing to design vaccines and targeted immunotherapies. We present a detailed analysis of CD205 expression, distribution and endocytosis in human monocyte-derived dendritic cells undergoing lipopolysaccharide-induced maturation. Unlike other members of the macrophage mannose receptor family, CD205 was up-regulated upon dendritic cell maturation. This increase was a result of de novo synthesis as well as a redistribution of molecules from endocytic compartments to the cell surface. Furthermore, the endocytic capacity of CD205 was abrogated and small amounts of the recently identified CD205-DCL-1 fusion protein were detected in mature DC. Our results suggest that CD205 has two distinct functions - one as an endocytic receptor on immature dendritic cells and a second as a non-endocytic molecule on mature dendritic cells - and further highlight its potential as an immuno-modulatory target for vaccine and immunotherapy development.