Overexpression of Foxn1 attenuates age-associated thymic involution and prevents the expansion of peripheral CD4 memory T cells

Erin C. Zook, Paulette A. Krishack, Shubin Zhang, Nancy J. Zeleznik-Le, Anthony B. Firulli, Pamela L. Witte, Phong T. Le

Research output: Contribution to journalArticle

75 Scopus citations

Abstract

The forkhead box n1 (Foxn1) transcription factor is essential for thymic organogenesis during embryonic development; however, a functional role of Foxn1 in the postnatal thymus is less well understood. We developed Foxn1 transgenic mice (Foxn1Tg), in which overexpression of Foxn1 is driven by the human keratin-14 promoter. Expression of the Foxn1 transgene increased the endogenous Foxn1 levels. In aged mice, overexpression of Foxn1 in the thymus attenuated the decline in thymocyte numbers, prevented the decline in frequency of early thymic progenitors, and generated a higher number of signal joint TCR excised circle. Histologic studies revealed that structural alterations associated with thymic involution were diminished in aged Foxn1 Tg. Total numbers of EpCAM + MHC II + and MHC II hi thymic epithelial cells were higher in young and old Foxn1Tg and more EpCAM + MHC II hi TEC expressed Ki-67 in aged Foxn1Tg compared with WT. Furthermore, Foxn1Tg displayed a significant reduction in the expansion of splenic CD4 + memory compartments and attenuated the decline in CD4 + and CD8 + naive compartments. Our data indicate that manipulation of Foxn1 expression in the thymus ameliorates thymopoiesis in aged mice and offer a strategy to combat the age-associated decline in naive T-cell production and CD4 naive/memory ratios in the elderly.

Original languageEnglish (US)
Pages (from-to)5723-5731
Number of pages9
JournalBlood
Volume118
Issue number22
DOIs
StatePublished - Nov 24 2011

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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