Declining expression of a single epithelial cell-autonomous gene accelerates age-related thymic involution

Liguang Sun, Jianfei Guo, Robert Brown, Takashi Amagai, Yong Zhao, Dong Ming Su

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Age-related thymic involution may be triggered by gene expression changes in lymphohematopoietic and/or nonhematopoietic thymic epithelial cells (TECs). The role of epithelial cell-autonomous gene FoxN1 may be involved in the process, but it is still a puzzle because of the shortage of evidence from gradual loss-of-function and exogenous gain-of-function studies. Using our recently generated loxP-floxed-FoxN1(fx) mouse carrying the ubiquitous CreERT (uCreERT) transgene with a low dose of spontaneous activation, which causes gradual FoxN1 deletion with age, we found that the uCreERT-fx/fx mice showed an accelerated age-related thymic involution owing to progressive loss of FoxN1+ TECs. The thymic aging phenotypes were clearly observable as early as at 3-6 months of age, resembling the naturally aged (18-22-month-old) murine thymus. By intrathymically supplying aged wild-type mice with exogenous FoxN1-cDNA, thymic involution and defective peripheral CD4+ T-cell function could be partially rescued. The results support the notion that decline of a single epithelial cell-autonomous gene FoxN1 levels with age causes primary deterioration in TECs followed by impairment of the total postnatal thymic microenvironment, and potentially triggers agerelated thymic involution in mice.

Original languageEnglish
Pages (from-to)347-357
Number of pages11
JournalAging cell
Volume9
Issue number3
DOIs
StatePublished - Jun 2010

Keywords

  • Spontaneous FoxN1 gene recombination
  • Thymic aging
  • Thymic epithelium
  • loxP/CreER system

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