Inactivation of the RB family prevents thymus involution and promotes thymic function by direct control of Foxn1 expression

Phillip M Garfin, Dullei Min, Jerrod L Bryson, Thomas Serwold, Badreddin Edris, Clare C Blackburn, Ellen R Richie, Kenneth I Weinberg, Nancy R Manley, Julien Sage, Patrick Viatour

Research output: Contribution to journalArticlepeer-review

Abstract

Thymic involution during aging is a major cause of decreased production of T cells and reduced immunity. Here we show that inactivation of Rb family genes in young mice prevents thymic involution and results in an enlarged thymus competent for increased production of naive T cells. This phenotype originates from the expansion of functional thymic epithelial cells (TECs). In RB family mutant TECs, increased activity of E2F transcription factors drives increased expression of Foxn1, a central regulator of the thymic epithelium. Increased Foxn1 expression is required for the thymic expansion observed in Rb family mutant mice. Thus, the RB family promotes thymic involution and controls T cell production via a bone marrow-independent mechanism, identifying a novel pathway to target to increase thymic function in patients.

Original languageEnglish
Pages (from-to)1087-1097
Number of pages11
JournalJournal of Experimental Medicine
Volume210
Issue number6
Early online date13 May 2013
DOIs
Publication statusPublished - 3 Jun 2013

Keywords

  • Animals
  • E2F Transcription Factors
  • Epithelial Cells
  • Epithelium
  • Forkhead Transcription Factors
  • Gene Silencing
  • Genes, Retinoblastoma
  • Mice
  • Mice, Inbred C57BL
  • Mutation
  • T-Lymphocytes
  • Thymus Gland

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