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

Beth Lucas, Andrea J. White, Emilie J. Cosway, Sonia M. Parnell, Kieran D. James, Nick D. Jones, Izumi Ohigashi, Yousuke Takahama, William E. Jenkinson and Graham Anderson ()
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Beth Lucas: University of Birmingham
Andrea J. White: University of Birmingham
Emilie J. Cosway: University of Birmingham
Sonia M. Parnell: University of Birmingham
Kieran D. James: University of Birmingham
Nick D. Jones: University of Birmingham
Izumi Ohigashi: University of Tokushima
Yousuke Takahama: National Institutes of Health
William E. Jenkinson: University of Birmingham
Graham Anderson: University of Birmingham

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-020-16041-x

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