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

Elife. 2022 Jan 19:11:e69088. doi: 10.7554/eLife.69088.

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/β-catenin signaling in mouse thymic epithelial cells (TECs) disrupts embryonic thymus organogenesis. However, the role of β-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 β-catenin highly specific in mouse TECs. We found that GOF of β-catenin in TECs results in severe thymic dysplasia and T-cell deficiency beginning from the embryonic period. By contrast, LOF of β-catenin in TECs reduces the number of cortical TECs and thymocytes modestly and only postnatally. These results indicate that fine-tuning of β-catenin expression within a permissive range is required for TECs to generate an optimal microenvironment to support postnatal T-cell development.

Keywords: T cell; TEC; Wnt; beta-catenin; immunology; inflammation; mouse; thymus.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Epithelial Cells / metabolism*
  • Female
  • Mice
  • T-Lymphocytes / metabolism*
  • Thymus Gland / metabolism*
  • beta Catenin / metabolism*

Substances

  • CTNNB1 protein, mouse
  • beta Catenin

Grants and funding

The funders had no role in study design, data collection, and interpretation, or the decision to submit the work for publication.