An Analysis of Trafficking Receptors Shows that CD44 and P-Selectin Glycoprotein Ligand-1 Collectively Control the Migration of Activated Human T-Cells.
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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DOI：
10.3389/fimmu.2017.00492
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发表时间：
2017
影响因子：
7.3
通讯作者：
Merzaban JS
中科院分区：
文献类型：
--
作者：
Ali AJ;Abuelela AF;Merzaban JS
选择素通过介导活化的T细胞的束缚和滚动到发炎的内皮上来引导活化的T细胞通过血流的交通，以这种方式充当信标以帮助将它们导航到炎症部位。在这里，我们提出了一个全面的分析E-选择素配体上表达的活化的人T细胞。我们发现了几种新的糖蛋白作为E-选择素配体的功能。具体而言，我们比较了P-选择素糖蛋白配体-I（PSGL-1）和CD 43（已知的E-选择素配体）与CD 44（先前未被表征为活化的人T细胞上的E-选择素配体的配体）的作用。我们发现，当在CD 4+和CD 8 + T细胞上表达时，CD 44充当功能性E-选择素配体。此外，CD 44蛋白携带将其鉴定为造血细胞E-和/或L-选择素配体（HCELL）的结合表位。此外，通过在原代活化的人T细胞中单独或一起敲除这些配体，我们证明了CD 44/HCELL而不是CD 43与PSGL-1作为主要的E-选择素配体合作。此外，我们通过显示来自银屑病患者分离的T细胞的CD 44/HCELL和PSGL-1而不是CD 43结合E-选择素，证明了我们的发现与慢性自身免疫性疾病的相关性。
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.