It's Time to Unite: Diversity and Coordination of Thymic Stromal Cells for T Cell Selection and Organ Integrity

The thymus is a primary lymphoid organ for generating a diverse yet self-tolerant T cell repertoire. Among the thymic stromal cells that create the thymic microenvironment, thymic epithelial cells (TECs) have received the most attention because of their distinctive functions in the repertoire selection of T cells. Other types of thymic stromal cells, such as fibroblasts and endothelial cells, have been less studied, and thus their thymus-specific nature and functions remain unclear. Recent advances in single-cell technologies, multicolor flow cytometry, and sophisticated mouse models have enabled the identification not only of TECs but also of non-TEC stromal cell diversity and the characterization of these cell subpopulations. This review provides a state-of-the-art overview of the thymic microenvironment, focusing on the development and functional diversity of TECs and non-TEC stromal cells. In particular, the recently discovered role of non-TEC stromal cells in thymic organogenesis, T cell selection, and involution and regeneration of the postnatal thymus is highlighted.