The thymus is the site of T cell development in vertebrates. In general, the output of T cells is determined by the number of thymic epithelial cells (TECs) and their relative thymopoietic activity. Here, we show that the thymopoietic activity of TECs differs dramatically between individual mouse strains. Moreover, in males of some strains, TECs perform better on a per cell basis than their counterparts in females; in other strains, this situation is reversed. Genetic crosses indicate that TEC numbers and thymopoietic capacity are independently controlled. Long-term analysis of functional parameters of TECs after castration provides evidence that the number of Foxn1-expressing TECs directly correlates with thymopoietic activity. Our study highlights potential complications that can arise when comparing parameters of TEC biology across different genetic backgrounds; these could affect the interpretation of the outcomes of interventions aimed at modulating thymic activity in genetically diverse populations, such as humans.
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http://dx.doi.org/10.1038/s41598-017-10746-8 | DOI Listing |
iScience
July 2024
Department of Developmental Immunology, Max Planck-Institute of Immunobiology and Epigenetics, Freiburg, Germany.
The thymus is a physiologically hypoxic organ and fulfills its role of generating T cells under low-oxygen conditions. We have therefore investigated how thymic epithelial cells (TECs) cope with physiological hypoxia by focusing on the role of the Hif1a-Vhl axis. In most cell types, the oxygen-labile transcriptional regulator Hif1a is a central player in co-ordinating responses to low oxygen: under normoxic conditions Hif1a is rapidly degraded in a Vhl-guided manner; however, under hypoxic conditions Hif1a is stabilized and can execute its transcriptional functions.
View Article and Find Full Text PDFCell Death Dis
May 2024
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
Within the thymus, thymic epithelial cells (TECs) create dedicated microenvironments for T cell development and selection. Considering that TECs are sensitive to distinct pathophysiological conditions, uncovering the molecular elements that coordinate their thymopoietic role has important fundamental and clinical implications. Particularly, medullary thymic epithelial cells (mTECs) play a crucial role in central tolerance.
View Article and Find Full Text PDFMar Drugs
October 2023
Department of Anatomy and Convergence Medical Sciences, Pusan National University College of Medicine, Yangsan 626-870, Republic of Korea.
Prolonged thymic involution results in decreased thymopoiesis and thymic output, leading to peripheral T-cell deficiency. Since the thymic-dependent pathway is the only means of generating fully mature T cells, the identification of strategies to enhance thymic regeneration is crucial in developing therapeutic interventions to revert immune suppression in immunocompromised patients. The present study clearly shows that fish collagen peptides (FCPs) stimulate activities of thymic epithelial cells (TECs), including cell proliferation, thymocyte adhesion, and the gene expression of thymopoietic factors such as FGF-7, IGF-1, BMP-4, VEGF-A, IL-7, IL-21, RANKL, LTβ, IL-22R, RANK, LTβR, SDF-1, CCL21, CCL25, CXCL5, Dll1, Dll4, Wnt4, CD40, CD80, CD86, ICAM-1, VCAM-1, FoxN1, leptin, cathepsin L, CK5, and CK8 through the NF-κB signal transduction pathway.
View Article and Find Full Text PDFJ Allergy Clin Immunol
November 2023
Department of Immunology, University of Texas Southwestern Medical Center, Dallas, Tex; Departments of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Tex; Microbiology, University of Texas Southwestern Medical Center, Dallas, Tex. Electronic address:
Background: Thymus hypoplasia due to stromal cell problems has been linked to mutations in several transcription factors, including Forkhead box N1 (FOXN1). FOXN1 supports T-cell development by regulating the formation and expansion of thymic epithelial cells (TECs). While autosomal recessive FOXN1 mutations result in a nude and severe combined immunodeficiency phenotype, the impact of single-allelic or compound heterozygous FOXN1 mutations is less well-defined.
View Article and Find Full Text PDFCommun Biol
September 2022
Department of Developmental Immunology, Max Planck-Institute of Immunobiology and Epigenetics, Stuebeweg 51, D-79108, Freiburg, Germany.
Few human tumours present with a recurrent pathognomonic mutation in a transcription factor. Thymomas are an exception, with the majority of some subtypes exhibiting a distinct somatically acquired missense mutation in the general transcription factor GTF2I. Co-dominant expression of wild-type and mutated forms of Gtf2i in the mouse thymic epithelium is associated with aberrant thymic architecture and reduced thymopoietic activity.
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