Endothelial CD130 controls the phenotype and function of High Endothelial Venules 3104

Abstract Description High Endothelial Venules (HEVs) are lined by specialized endothelial cells that mediate the selective recruitment of circulating immune cells to lymph nodes and Peyer’s patches. HEVs are normally absent from non-lymphoid tissues, but can be induced in settings of chronic inflammation and tumors. To date, the major contributor to HEVs formation is the lymphotoxin signaling pathway. Here, we show that endothelial CD130, the signaling subunit of cytokine receptors for the IL-6 family, is indispensable for the formation, function, and maintenance of HEVs. Deletion of endothelial CD130 resulted in a profound loss of HEVs morphology, abrogated expression of key HEV-specific traffic molecules, and severely compromised lymphocyte homing to lymph nodes and Peyer’s patches. A systematic evaluation of CD130 co-receptors, which confer cytokine binding specificity, identified LIFR, the receptor for leukemia inhibitory factor, as a major contributor to HEVs formation and function. Endothelial OSMR, the receptor for oncostatin M, controlled lymphocyte homing to Peyer’s patches. We conclude that endothelial CD130 signaling, primarily in response to LIF and OSM, is a key regulator of HEV phenotype and function. Pharmacologic manipulation of this pathway will offer new opportunities for anti-inflammatory and/or anti-tumoral therapies. Funding Sources NIH-NIAID AI112521 Topic Categories Cellular Adhesion, Migration, and Inflammation (CAM)