Foxn1 is required to maintain the postnatal thymic microenvironment in a dosage-sensitive manner

Lizhen Chen, Shiyun Xiao, Nancy R. Manley

Research output: Contribution to journalArticlepeer-review

163 Scopus citations


The postnatal thymus is the primary source of T cells in vertebrates, and many if not all stages of thymocyte development require interactions with thymic epithelial cells (TECs). The Foxn1 gene is a key regulator of TEC differentiation, and is required for multiple aspects of fetal TEC differentiation. Foxn1 is also expressed in the postnatal thymus, but its function after birth is unknown.We generated a Foxn1 allele with normal fetal expression and thymus development, but decreased expression in the postnatal thymus. This down-regulation causes rapid thymic compartment degeneration and reduced T-cell production. TEC subsets that express higher Foxn1 levels are most sensitive to its down-regulation, in particular MHCIIhiUEA-1 hi medullary TECs. The requirement for Foxn1 is extremely dosage sensitive, with small changes in Foxn1 levels having large effects on thymus phenotypes. Our results provide the first evidence that Foxn1 is required to maintain the postnatal thymus. Furthermore, the similarities of this phenotype to accelerated aging-related thymic involution support the possibility that changes in Foxn1 expression in TECs during aging contribute to the mechanism of involution.

Original languageEnglish (US)
Pages (from-to)567-574
Number of pages8
Issue number3
StatePublished - Jan 15 2009
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


Dive into the research topics of 'Foxn1 is required to maintain the postnatal thymic microenvironment in a dosage-sensitive manner'. Together they form a unique fingerprint.

Cite this