Abstract In many clinical situations which cause thymic involution and thereby result in immune
deficiency,
T cells are the most often affected, leading to a prolonged
deficiency of
T cells. Since only the thymic-dependent
T cell production pathway secures stable
regeneration of fully mature
T cells, seeking
strategies to enhance thymic
regeneration should be a key step in developing
therapeutic methods for the
treatment of these significant clinical problems. This study clearly shows that
receptor activator of NF-kappaB ligand (RANKL) stimulates
mouse thymic
epithelial cell activities including
cell proliferation,
thymocyte adhesion to thymic
epithelial cells, and the expression of
cell death regulatory genes favoring
cell survival,
cell adhesion molecules such as
ICAM-1 and
VCAM-1, and thymopoietic factors including
IL-7. Importantly, RANKL exhibited a significant capability to facilitate thymic
regeneration in
mice. In addition, this study demonstrates that RANKL acts directly on the
thymus to activate
thymus regeneration regardless of its potential influences on thymic
regeneration through an indirect or systemic effect. In
light of this, the present study provides a greater insight into the development of novel
therapeutic strategies for effective
thymus repopulation using RANKL in the design of
therapies for many clinical conditions in which
immune reconstitution is required.