Diversity in medullary thymic epithelial cells controls the activity and availability of iNKT cells

• DOI: 10.1038/s41467-020-16041-x
• Publication Date: 2020-05-04T10:05:01Z
• Authors: Beth Lucas; Andrea J. White; Emilie J. Cosway; Sonia M. Parnell; Kieran D. James; Nick D. Jones; Izumi Ohigashi; Yousuke Takahama; William E. Jenkinson; Graham Anderson
• Keywords: Mice, Knockout; Mice, Inbred BALB C; 0303 health sciences; Thymocytes; Science; T-Lymphocytes; Q; Cell Differentiation; Epithelial Cells; Dendritic Cells; Thymus Gland; Lymphocyte Activation; Article; Mice, Inbred C57BL; 03 medical and health sciences; Gene Expression Regulation; Lymphotoxin beta Receptor; Animals; Natural Killer T-Cells; Cell Lineage; Antigens, CD1d; Cell Proliferation; Signal Transduction

The thymus supports multiple αβ T cell lineages that are functionally distinct, but mechanisms control this multifaceted development poorly understood. Here we examine medullary thymic epithelial (mTEC) heterogeneity and its influence on CD1d-restricted iNKT cells. We find three distinct mTEClow subsets distinguished by surface, intracellular secreted molecules, identify LTβR as a cell-autonomous controller of their development. Importantly, mTEC enables the to differentially sublineages possessing effector properties. expression is essential for tuft cells which regulate NKT2 via IL-25, while controls CD104+CCL21+ capable IL-15-transpresentation regulating NKT1 NKT17. Finally, mTECs both iNKT-mediated activation dendritic cells, availability in extrathymic sites. In conclusion, specialization intrathymic function, determines pool size peripheral tissues.