Thymus and Parathyroid Organogenesis

The thymus is the principal site of T cell development and therefore is of central importance within the immune system: congenital athymia results in profound immunodeficiency, while perturbed thymic function can lead to autoimmunity. Although highly active in early life, the thymus undergoes premature involution, such that de novo T cell development diminishes significantly with age. This has implications for immune function in the aging population, and in clinical procedures such as bone marrow and solid organ transplantation, where thymic function is required for T cell reconstitution and/or tolerance induction. Interest therefore exists in enhancing immune reconstitution through regenerative or cell therapies for boosting thymus activity in vivo, or providing customized in vitro generated T cell repertoires for adoptive transfer. The success of such strategies is likely to depend on a detailed knowledge of the mechanisms regulating thymus development and homeostasis. Here, we review current understanding of cellular and molecular regulation of thymus organogenesis, focusing on the epithelial component of the thymic stroma which provides many of the specialist functions required to mediate T cell differentiation and T cell repertoire selection.