Foxn1 Protein Expression in the Developing, Aging, and Regenerating Thymus

The forkhead box N1 (Foxn1) protein is the key regulator of thymic epithelial cell (TEC) development, yet how Foxn1 functions remains largely unknown. All mature TECs arise from Foxn1-expressing progenitors/immature TECs and it is widely assumed that TECs as a whole are defined by Foxn1 expression....

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Published in:The Journal of immunology (1950) 2015-12, Vol.195 (12), p.5678-5687
Main Authors: Rode, Immanuel, Martins, Vera C, Küblbeck, Günter, Maltry, Nicole, Tessmer, Claudia, Rodewald, Hans-Reimer
Format: Article
Language:English
Subjects:
Aging - physiology
Animals
Cell Differentiation - drug effects
Cells, Cultured
Dexamethasone - pharmacology
Epithelial Cells - drug effects
Epithelial Cells - physiology
Fibroblast Growth Factor 7 - pharmacology
Forkhead Transcription Factors - genetics
Forkhead Transcription Factors - metabolism
Gene Expression Regulation, Developmental
Gene Knock-In Techniques
Humans
Mice
Mice, Inbred C57BL
Regeneration - physiology
Thymus Gland - physiology
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Summary:The forkhead box N1 (Foxn1) protein is the key regulator of thymic epithelial cell (TEC) development, yet how Foxn1 functions remains largely unknown. All mature TECs arise from Foxn1-expressing progenitors/immature TECs and it is widely assumed that TECs as a whole are defined by Foxn1 expression. However, data on the Foxn1 protein are virtually lacking. In this study, we developed novel tools to visualize Foxn1 protein expression at single-cell resolution. We generated Foxn1 knock-in mice expressing a C-terminal hemagglutinin-tagged Foxn1 protein, and a cytometry-grade monoclonal anti-Foxn1 Ab. We evaluated Foxn1 expression patterns in TEC subsets and its dynamics during normal thymus development, aging, injury, and regeneration. Upon challenges, upregulation of Foxn1 was a common feature of thymus regeneration, but the timing of Foxn1 expression changed and the responding TEC subsets depended on the type of treatment. Whereas dexamethasone and recombinant human fibroblast growth factor 7 promoted expansion of Foxn1(+)Ly51(+)CD80(-) TECs, castration led to expansion of Foxn1(+)Ly51(-)CD80(+) TECs. Collectively, Foxn1 expression is highly heterogeneous in the normal thymus, with large fractions of Foxn1(low) or Foxn1(-) TECs accumulating with age. Furthermore, Foxn1 expression is responsive to perturbations.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.1502010