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

Research output: Contribution to journalArticle

Authors

  • Andrea J. White
  • Sonia M. Parnell
  • Kieran D. James
  • Izumi Ohigashi
  • Yousuke Takahama
  • William E. Jenkinson

Colleges, School and Institutes

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.

Details

Original languageEnglish
Article number2198
JournalNature Communications
Volume11
Issue number1
Publication statusPublished - 4 May 2020

Keywords

  • Immunology, thymus, T-cell