Fine-tuning of β-catenin in thymic epithelial cells is required for postnatal T cell development

Abstract

In the thymus, the thymic epithelium provides a microenvironment essential for the development of functionally competent and self-tolerant T cells. Previous findings showed that modulation of Wnt/{beta}-catenin signaling in thymic epithelial cells (TECs) disrupts embryonic thymus organogenesis. However, the role of {beta}-catenin in TECs for postnatal T cell development remains to be elucidated. Here, we analyzed gain-of-function (GOF) and loss-of-function (LOF) of {beta}-catenin highly specific in TECs. We found that GOF of {beta}-catenin in TECs results in severe thymic dysplasia and T cell deficiency beginning from the embryonic period. By contrast, LOF of {beta}-catenin in TECs reduces the number of cortical TECs and thymocytes modestly and only postnatally. These results indicate that fine-tuning of {beta}-catenin expression within a permissive range is required for TECs to generate an optimal microenvironment to support postnatal T cell development.