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

Author

Listed:
  • 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)

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.

Suggested Citation

  • 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, 2020. "Diversity in medullary thymic epithelial cells controls the activity and availability of iNKT cells," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16041-x
    DOI: 10.1038/s41467-020-16041-x
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    Cited by:

    1. Fabian Klein & Clara Veiga-Villauriz & Anastasiya Börsch & Stefano Maio & Sam Palmer & Fatima Dhalla & Adam E. Handel & Saulius Zuklys & Irene Calvo-Asensio & Lucas Musette & Mary E. Deadman & Andrea , 2023. "Combined multidimensional single-cell protein and RNA profiling dissects the cellular and functional heterogeneity of thymic epithelial cells," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Beth Lucas & Andrea J. White & Fabian Klein & Clara Veiga-Villauriz & Adam Handel & Andrea Bacon & Emilie J. Cosway & Kieran D. James & Sonia M. Parnell & Izumi Ohigashi & Yousuke Takahama & William E, 2023. "Embryonic keratin19+ progenitors generate multiple functionally distinct progeny to maintain epithelial diversity in the adult thymus medulla," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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