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.
