Embryonic keratin19+ progenitors generate multiple functionally distinct progeny to maintain epithelial diversity in the adult thymus medulla

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. Jenkinson, Georg A. Hollander, Wei-Yu Lu and Graham Anderson ()
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Beth Lucas: University of Birmingham
Andrea J. White: University of Birmingham
Fabian Klein: University of Oxford
Clara Veiga-Villauriz: University of Oxford
Adam Handel: University of Oxford
Andrea Bacon: University of Birmingham
Emilie J. Cosway: University of Birmingham
Kieran D. James: University of Birmingham
Sonia M. Parnell: University of Birmingham
Izumi Ohigashi: Tokushima University
Yousuke Takahama: Experimental Immunology Branch, NCI/NIH
William E. Jenkinson: University of Birmingham
Georg A. Hollander: University of Oxford
Wei-Yu Lu: University of Edinburgh
Graham Anderson: University of Birmingham

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: Abstract The thymus medulla is a key site for immunoregulation and tolerance, and its functional specialisation is achieved through the complexity of medullary thymic epithelial cells (mTEC). While the importance of the medulla for thymus function is clear, the production and maintenance of mTEC diversity remains poorly understood. Here, using ontogenetic and inducible fate-mapping approaches, we identify mTEC-restricted progenitors as a cytokeratin19+ (K19+) TEC subset that emerges in the embryonic thymus. Importantly, labelling of a single cohort of K19+ TEC during embryogenesis sustains the production of multiple mTEC subsets into adulthood, including CCL21+ mTEClo, Aire+ mTEChi and thymic tuft cells. We show K19+ progenitors arise prior to the acquisition of multiple mTEC-defining features including RANK and CCL21 and are generated independently of the key mTEC regulator, Relb. In conclusion, we identify and define a multipotent mTEC progenitor that emerges during embryogenesis to support mTEC diversity into adult life.

Date: 2023
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37589-4

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DOI: 10.1038/s41467-023-37589-4

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