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首页> 美国卫生研究院文献>other >An Analysis of Trafficking Receptors Shows that CD44 and P-Selectin Glycoprotein Ligand-1 Collectively Control the Migration of Activated Human T-Cells
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An Analysis of Trafficking Receptors Shows that CD44 and P-Selectin Glycoprotein Ligand-1 Collectively Control the Migration of Activated Human T-Cells

机译：贩运受体的分析表明CD44和P-选择蛋白糖蛋白配体1共同控制活化的人类T细胞的迁移。

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Selectins guide the traffic of activated T-cells through the blood stream by mediating their tethering and rolling onto inflamed endothelium, in this way acting as beacons to help navigate them to sites of inflammation. Here, we present a comprehensive analysis of E-selectin ligands expressed on activated human T-cells. We identified several novel glycoproteins that function as E-selectin ligands. Specifically, we compared the role of P-selectin glycoprotein ligand-1 (PSGL-1) and CD43, known E-selectin ligands, to CD44, a ligand that has not previously been characterized as an E-selectin ligand on activated human T-cells. We showed that CD44 acts as a functional E-selectin ligand when expressed on both CD4+ and CD8+ T-cells. Moreover, the CD44 protein carries a binding epitope identifying it as hematopoietic cell E- and/or L-selectin ligand (HCELL). Furthermore, by knocking down these ligands individually or together in primary activated human T-cells, we demonstrated that CD44/HCELL, and not CD43, cooperates with PSGL-1 as a major E-selectin ligand. Additionally, we demonstrated the relevance of our findings to chronic autoimmune disease, by showing that CD44/HCELL and PSGL-1, but not CD43, from T-cells isolated from psoriasis patients, bind E-selectin.
机译：选择素通过介导它们的束缚并滚动到发炎的内皮上来引导活化的T细胞通过血流的流动，以这种方式充当信标，帮助其导航至炎症部位。在这里，我们目前对激活的人类T细胞上表达的E-选择素配体进行全面分析。我们确定了几种新型糖蛋白，可作为E-选择蛋白配体。具体来说，我们将P-选择蛋白糖蛋白配体-1（PSGL-1）和CD43（已知的E-选择蛋白配体）与CD44（先前尚未表征为活化的人T-素的E-选择蛋白配体）的作用进行了比较细胞。我们表明，CD44在CD4 + 和CD8 + T细胞上均表达时，可作为功能性E-选择蛋白配体。而且，CD44蛋白带有结合表位，将其鉴定为造血细胞E-和/或L-选择蛋白配体（HCELL）。此外，通过敲除这些配体单独或一起在原代活化的人T细胞中敲除，我们证明CD44 / HCELL而非CD43与PSGL-1作为主要的E-选择蛋白配体协同作用。此外，我们通过证明牛皮癣患者分离的T细胞中的CD44 / HCELL和PSGL-1（而非CD43）结合E-选择素，证明了我们的发现与慢性自身免疫疾病的相关性。

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