Border control: Anatomical origins of the thymus medulla

The thymus is an anatomically compartmentalized primary lymphoid organ that fosters the production of self-tolerant T cells. The thymic cortex provides a specialized microenvironment in which cortical thymic epithelial cells (cTECs) support the positive selection and further differentiation of self-MHC-restricted thymocytes. Following their migration into the medulla, positively selected thymocytes are further screened for self-reactivity, which involves both negative selection and Foxp3(+) regulatory T cell generation via interactions with medullary thymic epithelial cells (mTECs). Given the importance of both cortical and medullary microenvironments for T cell development, studies that address the developmental origins of cTECs and mTECs are important in understanding the processes that shape the developing T cell receptor repertoire, and reduce the frequency of self-reactive T cells that initiate autoimmune disease. In this issue of the European Journal of Immunology, Onder et al. [Eur. J. Immunol. 2015. 45: 2218-2231] identified a subset of podoplanin(+) mTECs in mice that reside at the corticomedullary junction (CMJ), show that their development is important to establish self-tolerance, and require the presence of self-reactive T cells. Collectively, their findings highlight the CMJ as a potential repository for precursors of the mTEC lineage, and provide a better understanding of thymus medulla formation.