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

Fujimori, S.; Ohigashi, I.; Abe, H.; Taketo, M. M.; Takahama, Y.; Takada, S.

doi:10.1101/2021.05.02.442353

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bioRxiv · 10.1101/2021.05.02.442353

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

Fujimori, S.·Ohigashi, I.·Abe, H.·Taketo, M. M.·Takahama, Y.·Takada, S.

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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.

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Fujimori, S., Ohigashi, I., Abe, H., Taketo, M. M., Takahama, Y., Takada, S.. 2021-05-02. Fine-tuning of β-catenin in thymic epithelial cells is required for postnatal T cell development. https://doi.org/10.1101/2021.05.02.442353

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