title: Foxn1 Protein Expression in the Developing, Aging, and Regenerating Thymus.
abstract: 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.
authors.affiliation: Division of Cellular Immunology, German Cancer Research Center, D-69120 Heidelberg, Germany; and i.rode@dkfz.de hr.rodewald@dkfz.de.
authors.forename: Immanuel
authors.initials: I
authors.lastname: Rode
authors.affiliation: Division of Cellular Immunology, German Cancer Research Center, D-69120 Heidelberg, Germany; and.
authors.forename: Vera C
authors.identifier: http://orcid.org/0000-0001-8717-9709
authors.initials: VC
authors.lastname: Martins
authors.affiliation: Division of Cellular Immunology, German Cancer Research Center, D-69120 Heidelberg, Germany; and.
authors.forename: Günter
authors.initials: G
authors.lastname: Küblbeck
authors.affiliation: Division of Cellular Immunology, German Cancer Research Center, D-69120 Heidelberg, Germany; and.
authors.forename: Nicole
authors.initials: N
authors.lastname: Maltry
authors.affiliation: Genomics and Proteomics Core Facility, Monoclonal Antibody Facility, German Cancer Research Center, D-69120 Heidelberg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Tessmer
authors.affiliation: Division of Cellular Immunology, German Cancer Research Center, D-69120 Heidelberg, Germany; and i.rode@dkfz.de hr.rodewald@dkfz.de.
authors.forename: Hans-Reimer
authors.initials: HR
authors.lastname: Rodewald
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology*; D051523:Fibroblast Growth Factor 7 / Q000494:pharmacology; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D055879:Gene Knock-In Techniques; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D012038:Regeneration / Q000502:physiology; D013950:Thymus Gland / Q000502:physiology*
chemical_list: D051858:Forkhead Transcription Factors; C090140:Whn protein; D051523:Fibroblast Growth Factor 7; D003907:Dexamethasone