Protein O‐Glycosylation Shapes Lymphatic Endothelia and Lymph Node Macrophage Populations

Endothelial cells were among the first cells identified to have a surface glycocalyx, but its functions are still elusive. Within the glycocalyx are many glycoproteins whose O-glycosylation is partly regulated by Cosmc, an essential chaperone for functional activity of T-synthase that adds galactose to O-glycans initiating their elongation. Using mice with inducible deletion of either Cosmc (C1Galt1C1) or the sialyltransferase St3Gal-1 in lymphatic endothelial cells (LEC), we discovered that loss of elongated O-glycans is accompanied by major changes in glycoprotein composition, including podoplanin, CD44, Lyve-1, and ICAM-1. These changes in the endothelial glycocalyx are sensed by adhesion molecules, such as Siglec-1, and lead to major changes in the size and phenotype of lymph node macrophage populations. Our findings demonstrate the crucial roles of O-glycosylation in regulating LEC functions and lymph node macrophage differentiation.