Laminin-Mediated Interactions in Thymocyte Migration and Development

In this review, the authors highlight the role of laminin isoforms for intrathymic T-cell migration and maturation in both physiological and pathological conditions. Intrathymic T-cell differentiation is a key process for the development and maintenance of cell-mediated immunity. Here, the authors propose a multivectorial model for describing intrathymic thymocyte migration. One of the individual vectors comprises interactions mediated by laminins. Several different laminin isoforms are expressed in the thymus, produced mainly by thymic epithelial cells (TECs). Thymocytes and epithelial cells express integrin-type laminin receptors. It has been reported that a mutant mouse that lack laminin-211 exhibits defective thymocyte differentiation. Several data also show haptotactic effects of laminin upon thymocytes and their adhesion on TECs. Interestingly, laminin synergizes with chemokines to enhance thymocyte migration. More recently, the authors show that knocking down the ITGA6 gene (which encodes the α6 integrin chain of laminin receptors) in human TECs modulates a large number of cell migration-related genes and results in changes of adhesion pattern of thymocytes into the thymic epithelium. Overall, laminin-mediated interactions can be placed at the cross-road of the multivectorial process of thymocyte migration, with a direct influence per se, as well as by modulating other molecular interactions associated with the intrathymic-trafficking events.