Additional roles of ephrins in immunity Sample Clauses

Additional roles of ephrins in immunity. In addition to the role that the eph/ephrin signalling pathway plays in lymphatic development and maintenance, it has more recently become implicated in other settings. The eph family of neuronal guidance molecules and their ligands, the ephrins, are the most abundant group of receptor tyrosine kinases in the mammalian genome. The role they play in embryogenesis and cancer pathology has been well established; however, they are now being implicated in inflammation and immunity. Expression of ephs and ephrins across cell types is varied, and signalling can occur either through the receptor (forward) or the ligand (reverse) (118). Eph/ephrin signalling most commonly results in changes in cell motility; either repulsion or adhesion of cells to guide in the organisation of cells in developing tissue, or during de novo growth such as in lymphangiogenesis (102). In addition to patterning responses, signalling via the eph/ephrin pathway can affect cell differentiation, proliferation and gene expression (118), further indicating a potential role in chronic inflammation. Enhanced expression of ephrin B2 has been found on the blood endothelium in areas of atherosclerotic plaque formation, where it was found to aid adhesion and transmigration of infiltrating monocytes which express the ephB4 receptor (119). Also, addition of immobilized ephrin B2 to monocytes in culture caused them to upregulate expression of chemokine (c-c motif) ligand (CCL) 21 (119). In fact, many leukocytes express ephrins, and have been found to modulate their expression in response to pro-inflammatory signals such as TNF-α (120). In particular, ephrin B2 has been demonstrated as a co- stimulatory molecule for T cells (121). In the study by Xx at al. ephrin B2 mRNA was found to be expressed in the white pulp of the spleen and the cortex of the thymus. At the protein level it was found to be expressed on the surface of T cells and monocytes, whereas its receptors were mainly found on T cells. T-cell stimulation could be induced using solid phase ephrin B2 and sub-optimal amounts of CD3. This led to the production of IFN-γ and enhanced cytotoxic activity of CD8+ T cells. Evidence was also provided for ephrin B2 localisation in the immunological synapse, linking it directly with T-cell co- stimulation (121).