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

J Exp Med
Publication Year: 
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
PubMed link: 
Public Summary: 
Scientific 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.