Abstract
The thymus is the site of T cell development and selection. In addition to lymphocytes, the thymus is composed of several types of stromal cells that are exquisitely organized to create the appropriate environment and microenvironment to support the development and selection of maturing T cells. Thymic epithelial cells (TECs) are one of the more important cell types in the thymic stroma, and they play a critical role in selecting functional T cell clones and supporting their development. In this study, we used a mouse genetics approach to investigate the consequences of deleting the Pten tumor suppressor gene in the TEC compartment of the developing thymus. We found that PTEN deficiency in TECs results in a smaller thymus with significantly disordered architecture and histology. Accordingly, loss of PTEN function also results in decreased T cells with a shift in the distribution of T cell subtypes towards CD8+ T cells. These experiments demonstrate that PTEN is critically required for the development of a functional thymic epithelium in mice. This work may help better understand the effects that certain medical conditions or clinical interventions have upon the thymus and immune function.
Highlights
As the site of T cell maturation and selection, the thymus is essential for proper function of the immune system [1]
In order to evaluate the effect of loss of PTEN in thymic epithelial cells on thymus size and function, we crossed mice that express the Cre recombinase under the control of the Foxn1 promoter (Foxn1-Cre) with conditional mutant Pten mice (Ptenlox/lox)
This genotype enables the inactivation of the PTEN protein in cells that express Foxn1, such as thymic epithelial cells (TECs) and skin keratinocytes
Summary
As the site of T cell maturation and selection, the thymus is essential for proper function of the immune system [1]. In their migration through the thymus, T cells interact with several different cell types [2]. One of the important cell types, thymic epithelial cells (TECs), plays a central role in the establishment and the maintenance of the thymic microenvironment that supports T cell maturation and selection [2, 3]. The mechanisms controlling thymic development and involution are still poorly understood, limiting the development of therapeutic approaches to improve immune function in a PLOS ONE | DOI:10.1371/journal.pone.0149430 February 25, 2016
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