Projects per year
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.
Original language | English |
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Article number | 2198 |
Number of pages | 14 |
Journal | Nature Communications |
Volume | 11 |
Issue number | 1 |
Early online date | 4 May 2020 |
DOIs | |
Publication status | Published - Dec 2020 |
Keywords
- Immunology
- thymus
- T-cell
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Dive into the research topics of 'Diversity in medullary thymic epithelial cells controls the activity and availability of iNKT cells'. Together they form a unique fingerprint.Projects
- 1 Finished
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Understanding the regulation of thymus function to control self-tolerant T-cell production
1/10/15 → 30/09/20
Project: Research Councils