Submitted April 11, 2008
Accepted July 29, 2008
Maintenance of a normal thymic microenvironment and T cell homeostasis require Smad4-mediated signalling in thymic epithelial cells
Lukas T Jeker, Thomas Barthlott, Marcel P Keller, Saulius Zuklys, Mathias Hauri-Hohl, Chu-Xia Deng, and Georg A Hollander*
Department of Biomedicine, Laboratory of Pediatric Immunology, University of Basel and The University Children's Hospital (UKBB), Basel, Switzerland
Genetics of Development and Disease Branch, NIDDK, National Institutes of Health, Bethesda, Maryland, United States
* Corresponding author; email: georg-a.hollaender{at}unibas.ch.
Signals mediated by the transforming growth factor 
(TGF-) super-family of growth factors have been implicated in thymic epithelial cell (TEC) differentiation, homeostasis and function but a direct reliance on these signals has not been established. Here we demonstrate that a block in canonical TGF- signalling by the loss of Smad4 expression in TECs leads to qualitative changes in TEC function and a progressively disorganized thymic microenvironment. Moreover, the number of thymus resident early T lineage progenitors (ETPs) is severely reduced in the absence of Smad4 expression in TECs and directly correlates with extensive thymic and peripheral lymphopenia. Our observations hence place Smad4 within the signalling events in TECs that determine total thymus cellularity by controlling the number of ETPs.
