Lucas, Beth University of Birmingham
White, Andrea J. University of Birmingham
Cosway, Emilie J. University of Birmingham
Parnell, Sonia M. University of Birmingham
James, Kieran D. University of Birmingham
Jones, Nick D. University of Birmingham
Ohigashi, Izumi University of Tokushima Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Takahama, Yousuke National Institutes of Health Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Jenkinson, William E. University of Birmingham
Anderson, Graham University of Birmingham
The thymus supports multiple αβ T cell lineages that are functionally distinct, but mechanisms that control this multifaceted development are poorly understood. Here we examine medullary thymic epithelial cell (mTEC) heterogeneity and its influence on CD1d-restricted iNKT cells. We find three distinct mTEClow subsets distinguished by surface, intracellular and secreted molecules, and identify LTβR as a cell-autonomous controller of their development. Importantly, this mTEC heterogeneity enables the thymus to differentially control iNKT sublineages possessing distinct effector properties. mTEC expression of LTβR is essential for the development thymic tuft cells which regulate NKT2 via IL-25, while LTβR controls CD104+ CCL21+ mTEClow that are capable of IL-15-transpresentation for regulating NKT1 and NKT17. Finally, mTECs regulate both iNKT-mediated activation of thymic dendritic cells, and iNKT availability in extrathymic sites. In conclusion, mTEC specialization controls intrathymic iNKT cell development and function, and determines iNKT pool size in peripheral tissues.
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Institute of Advanced Medical Sciences