Thymic Epithelial Cells

TLDR

Thymic epithelial cells are essential for guiding T‑cell development, exhibiting diverse phenotypes that bias thymocytes toward self‑tolerance, and their dysfunction is linked to autoimmune and immunodeficiency disorders. The authors aim to evaluate TECs as targets for cell therapies to restore immune function. They review recent advances in the cellular and molecular mechanisms governing TEC development, function, dysfunction, and regeneration.

Abstract

Intrathymic T cell development is a complex process that depends upon continuous guidance from thymus stromal cell microenvironments. The thymic epithelium within the thymic stroma comprises highly specialized cells with a high degree of anatomic, phenotypic, and functional heterogeneity. These properties are collectively required to bias thymocyte development toward production of self-tolerant and functionally competent T cells. The importance of thymic epithelial cells (TECs) is evidenced by clear links between their dysfunction and multiple diseases where autoimmunity and immunodeficiency are major components. Consequently, TECs are an attractive target for cell therapies to restore effective immune system function. The pathways and molecular regulators that control TEC development are becoming clearer, as are their influences on particular stages of T cell development. Here, we review both historical and the most recent advances in our understanding of the cellular and molecular mechanisms controlling TEC development, function, dysfunction, and regeneration.