Wnt signaling during thymic involution and reconstitution. (HEM7P.226)

Abstract

Abstract Despite its critical role in T-cell development, the thymus undergoes profound age-related involution. Inhibition of Wnt signaling in thymic epithelium (TECs) leads to rapid involution. Lack of a Wnt reporter that was functional in TECs hindered characterization of Wnt signaling during TEC ontogeny. Using the TCF/LEF-H2BGFP Wnt reporter mouse, TECs undergoing active Wnt signaling were characterized during different stages of thymic aging and recovery. In the postnatal thymus, H2BGFP expression was restricted to TECs in the medulla and CMJ including 60% of the Aire-expressing mTECs, suggesting a role for Wnt signaling in the development of this critical TEC subset. Comparison of the TECs undergoing Wnt signaling in old versus young thymus revealed an increase in the frequency of TECs undergoing Wnt signaling even though overall TEC numbers decreased significantly with age. The decrease in both total TECs and TECs undergoing Wnt signaling was most apparent in the UEA1hi mTEC subset and suggests that the age related decline in AIRE expression is correlated with the decline in mTECs undergoing Wnt signaling. SCID/TCF/LEF1-H2BGFP mice were used to observe Wnt signaling during thymic reconstitution induced by either bone marrow transplant (BMT) (full thymic development) or injection of mature T cells (mTEC development). During thymic reconstitution induced by both BMT and mature T-cells, Wnt signaling was primarily associated with Aire expressing mTECs, critical for self-tolerance.