FOXN1 in thymus organogenesis and development

HJ Vaidya, A Briones Leon… - European journal of …, 2016 - Wiley Online Library
HJ Vaidya, A Briones Leon, CC Blackburn
European journal of immunology, 2016Wiley Online Library
Development of the primary T‐cell repertoire takes place in the thymus. The linked
processes of T‐cell differentiation and T‐cell repertoire selection each depend on
interactions between thymocytes and thymic stromal cells; in particular, with the epithelial
cells of the cortical and medullary thymic compartments (cortical and medullary thymic
epithelial cells; cTECs and mTECs, respectively). The importance of the thymic epithelial cell
lineage in these processes was revealed in part through analysis of nude (nu/nu) mice …
Development of the primary T‐cell repertoire takes place in the thymus. The linked processes of T‐cell differentiation and T‐cell repertoire selection each depend on interactions between thymocytes and thymic stromal cells; in particular, with the epithelial cells of the cortical and medullary thymic compartments (cortical and medullary thymic epithelial cells; cTECs and mTECs, respectively). The importance of the thymic epithelial cell lineage in these processes was revealed in part through analysis of nude (nu/nu) mice, which are congenitally hairless and athymic. The nude phenotype results from null mutation of the forkhead transcription factor FOXN1, which has emerged as a pivotal regulator both of thymus development and homeostasis. FOXN1 has been shown to play critical roles in thymus development, function, maintenance, and even regeneration, which positions it as a master regulator of thymic epithelial cell (TEC) differentiation. In this review, we discuss current understanding of the regulation and functions of FOXN1 throughout thymus ontogeny, from the earliest stages of organogenesis through homeostasis to age‐related involution, contextualising its significance through reference to other members of the wider Forkhead family.
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