Abstract
In the thymus, cortical and medullary thymic epithelial cells (TECs) are instrumental for generating a repertoire of functional T cells. Hence, there has been much interest in the ontogeny of TECs. While medullary TEC (mTEC) and bipotent progenitors have been identified, the existence of a cortical TEC (cTEC) progenitor remains ambiguous. In this study, we used lineage tracing based on a target gene of the Wnt pathway, Axin2. We found that Axin2 initially labels cells in both the cortical and medullary compartments. Using Axin2-CreERT2 mice to track the fate of labelled cells, we identified long-lived cortical TEC progenitors that give rise to expanding clones and contribute to homeostasis in postnatal thymus. In contrast, no clonal expansion was found in the medullary or in the K5K8-double positive compartments. The identification of cTEC progenitors and their regulation by Wnt signaling have important implications for our understanding of thymus physiology during homeostasis and TEC-related disorders.
Highlights
In jawed vertebrates, the thymus is a critical site where immunity is established [1]
We observed rare mGFP-labeled cells with a circular morphology, distinct from thymic epithelial cells (TECs)’ stellate morphology (Fig 1E, dotted circle). As these labeled cells were absent from the thymus after one month of tracing, we focused on Axin2-expressing TECs that persisted in the thymic epithelium over the long term
We demonstrate the existence of cortical TEC (cTEC) progenitor in the postnatal thymus through lineage tracing with AXCT2 mice
Summary
The thymus is a critical site where immunity is established [1]. Immature thymocytes home to the thymus and begin the intricate process of expansion and selection, eventually emerging as functional T lymphocytes that perform cellmediated immunity. T lymphocyte maturation process is orchestrated by stromal thymic epithelial cells (TECs), which guide migrating thymocytes to undergo negative and positive selection [1]. Defects in TECs can lead to pathologies like immune deficiency or autoimmune diseases like Myasthenia gravis [2], underscoring the importance of TECs in ensuring proper development of the immune system. While the identities of the embryonic TEC stem and progenitors have been established [3], comparable knowledge about postnatal TECs is just starting to emerge. The TECs that reside within each compartment are functionally different, and are termed
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