CD44 and PSGL-1 Collaborate in Controlling the Migration of Human Activated T-Cells

• Published in: Blood 2015-12, Vol.126 (23), p.3429-3429
• Main Authors: Ali, Amal J., Merzaban, Jasmeen S., Abuelela, Ayman F.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V126.23.3429.3429

Selectins play a central role in the trafficking of activated T cells by mediating tethering and rolling on vascular endothelium, acting as a beacon to help navigate them to the site of infection. Here we present a comprehensive binding and in vitro functional analysis of E-selectin ligands expressed on human activated T cells. Using a mass-spectrometric approach we identified a number of glycoproteins that may act as physiological E-selectin ligands on human activated T cells and focused on comparing the role the previously identified well-known E-selectin ligands, PSGL-1 (P-selectin glycoprotein ligand 1) to the newly identified ligand CD44. We show that CD44 from human activated CD4+ and CD8+ T cells binds E-selectin, and that immobilized CD44 mediates tethering and rolling of E-selectin expressing CHO cells via sialylated N-linked glycans. By knocking down CD44 and/or PSGL-1 in primary human activated T cells, our data demonstrate for the first time that CD44 is essential for mediating the rolling over E-selectin and thereby cooperates with PSGL-1 as a major E-selectin ligand on human activated T cells. This has major implications in the development of targeted therapies to combat inflammatory diseases and in transplantation settings. No relevant conflicts of interest to declare.