The
thymus is a lymphoid-epithelial organ whose main function is to generate
naïve T cells
for
the peripheral T cell pool; nevertheless, the production of naïve T
cells deteriorates with
age, a condition known as thymic involution. Our laboratory is
interested in understanding
the
molecular mechanisms by which thymic epithelial cells (TEC) affect T
cell development
in the normal setting and in the context of the aged thymus. We
hypothesize that
TEC-T cell progenitor interaction orchestrates the coordinated
expression of a combinatory
set
of transcription factors that affect progenitors lineage commitment and
differentiation.
Aging in the thymus is affected by the changes at the apex of TEC-T cell
progenitor
interaction
resulting in the decline in thymopoiesis. Thus, the critical steps
toward
understanding the mechanism of aging in the thymus are to identify these
changes in
molecular terms and then to determine whether these alterations lead to
a decline in naïve
T
cell output.
Based on our observation that expression of the TEC specific the
transcription factor
FoxN1, which is essential for functional maturation of TEC, is
significantly reduced with
age, we have generated transgenic mice that overexpress FoxN1. These
mice show the
absence of several age-associated changes in thymic involution such as
reduced naïve
T
cell output, number of T cell progenitors and T cell precursor. The
mouse model
provides us a novel animal model to discover the molecular mechanism
that affects
thymic involution.
