The Murine Epithelial Thymic Microenvironment Is Governed by Eph/Ephrin Signalling

Although the relevance of thymic epithelial cell–thymocyte interactions for thymus function has long been emphasised, the mechanisms that govern the biology of thymic epithelial cells (TECs) are not fully understood. In other epithelial tissues, erythropoietin-producing hepatocellular carcinoma (Eph) receptors and their ligands, the Eph receptor-interacting proteins (ephrins), have been demonstrated to be important regulators of epithelial homeostasis. Accordingly, we have studied the function of Eph/ephrin signalling in the organisation, phenotypes and function of mouse thymic epithelial cells, as well as its effects on T-cell differentiation, for over 20 years. This review provides a detailed description of these results, concluding that the absence of certain EphA/B receptors or ephrins B generates specific phenotypes that affect T-cell differentiation and immunological function in different ways. This suggests that the proper histological organisation of the epithelial thymic stroma is not essential for normal T-cell maturation, or that at least some aspects of the process are preserved.