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J Immunol:C型凝集素影响树突细胞迁移

来源:生物谷 2016-06-23 10:00

 

2016年6月23日 讯 /生物谷BIOON/ --免疫细胞表面有很多不同的模式识别受体,用以识别来自病原体或者受损伤细胞的特定分子结构,其中最主要的一类就是C type Lectin受体(CLR)。虽然绝大部分CLR在与碳水化合物配体结合时依赖钙离子,但也有一些可以在不依赖钙离子的前提下进行,另外还有一些CLR能够与蛋白质以及脂类结合。CLR信号参与了免疫细胞的多种功能,包括细胞迁移,粘附以及淋巴结的扩张或收缩等等。

CD302是最近发现的一类新型的CLR,是最简单的I型跨膜蛋白。CD302主要表达于肺脏、PBMC以及脾脏等组织的髓系细胞中,比如单核细胞、巨噬细胞、DC等等。激活后的细胞CD302的表达量会发生下调。此前研究发现CD302与胞内的细胞骨架具有空间上的相关性,这表明CD302可能参与了细胞的年付以及迁移过程。

目前还没有找到CD302的确切配体分子,但是已有的结果表明CD302不具有典型的CLR的糖类结合的能力。另外,CD302与其它CLR相似,具有促进抗体介导的内吞作用的能力。

针对CD302的具体功能,来自澳大利亚悉尼ANZAC研究所的Derek N. J. Hart课题组进行了深入研究,相关结果发表在最近一期的《Journal of Immunology》杂志上。

首先,作者检测了小鼠不同组织中CD302的表达水平,结果显示,CD302在小鼠中的表达分布与在人体内的相似,及主要表达于肺脏、脾脏以及PBMC中。另外,作者发现迁移的DC中CD302的表达量明显高于不迁移的DC。进一步,作者发现CXD302的表达与CD68阳性的免疫细胞具有很强的相关性。

之后,作者构建了CD302缺失突变体小鼠。通过比较其与野生型小鼠,作者发现突变体小鼠中DC的迁移能力发生了明显的下降。

最后,作者通过免疫荧光成像的方式发现CD302的缺失能够降低DC向淋巴结迁移的能力,而且CD8效应T细胞的反应也受到了明显的抑制。(生物谷bioon.com)

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doi: 10.4049/jimmunol.1600259

PMC:

PMID:

Characterization of the Expression and Function of the C-Type Lectin Receptor CD302 in Mice and Humans Reveals a Role in Dendritic Cell Migration

Tsun-Ho Lo, Pablo A. Silveira, Phillip D. Fromm, Nirupama D. Verma, Phi A. Vu, Fiona Kupresanin, Rhonda Adam, Masato Kato, Victoria C. Cogger, Georgina J. Clark and Derek N. J. Hart

C-type lectin receptors play important roles in immune cell interactions with the environment. We described CD302 as the simplest, single domain, type I C-type lectin receptor and showed it was expressed mainly on the myeloid phagocytes in human blood. CD302 colocalized with podosomes and lamellopodia structures, so we hypothesized that it played a role in cell adhesion or migration. In this study, we used mouse models to obtain further insights into CD302 expression and its potential immunological function. Mouse CD302 transcripts were, as in humans, highest in the liver, followed by lungs, lymph nodes (LN), spleen, and bone marrow. In liver, CD302 was expressed by hepatocytes, liver sinusoidal endothelial cells, and Kupffer cells. A detailed analysis of CD302 transcription in mouse immune cells revealed highest expression by myeloid cells, particularly macrophages, granulocytes, and myeloid dendritic cells (mDC). Interestingly, 2.5-fold more CD302 was found in migratory compared with resident mDC populations and higher CD302 expression in mouse M1 versus M2 macrophages was also noteworthy. CD302 knockout (CD302KO) mice were generated. Studies on the relevant immune cell populations revealed a decrease in the frequency and numbers of migratory mDC within CD302KO LN compared with wild-type LN. In vitro studies showed CD302KO and wild-type DC had an equivalent capacity to undergo maturation, prime T cells, uptake Ags, and migrate toward the CCL19/CCL21 chemokines. Nevertheless, CD302KO migratory DC exhibited reduced in vivo migration into LN, confirming a functional role for CD302 in mDC migration.

 
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