Eph and ephrin: Key molecules for the organization and function of the thymus gland

Eph are the largest family of protein tyrosine kinases, which are described in most cell types. Together with their ligands, ephrins, Eph participate in the organogenesis of many tissues mediating numerous processes, such as cell positioning and cell migration, which are key for the functioning of the thymus: a primary lymphoid organ involved in T-cell maturation. In the present study, we review available data on the role played by these families of molecules in the biology of the thymus gland. Most Eph and ephrin are expressed in adult and fetal thymus, frequently in both thymocytes and thymic stromal cells. They appear to play an essential role in governing thymus size through the control of survival of thymocytes and thymic epithelial cells (TEC). Furthermore, studies in vivo and in vitro demonstrate that altered Eph/ephrin signalling results in specific thymus phenotypes and conclude that the balance of Eph/ephrin signals finally determine the pattern of maturation/differentiation of thymocytes and TEC. Indeed, the role of Eph/ephrin in thymus function appears early in ontogeny. In this regard, several results emphasize their relevance in key processes for thymus organization, such as the recruitment of lymphoid progenitors to the thymic primordium, the branching pattern of thymus epithelium and the positioning of thymocytes and TEC in the growing gland. Some of the phenotypic alterations observed in the thymus of Eph/ephrin deficient mice are reflected in the peripheral lymphoid organs, but there is no evidence for alterations in the function of their immune systems.