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Abstract
Glucocorticoids are widely used immunosuppressive drugs in treatment of autoimmune diseases and hematological malignancies. Glucocorticoids are particularly effective immune suppressants, because they induce rapid peripheral T cell and thymocyte apoptosis resulting in impaired T cell-dependent immune responses. Although glucocorticoids can induce apoptotic cell death directly in developing thymocytes, how exogenous glucocorticoids affect the thymic epithelial network that provides the microenvironment for T cell development is still largely unknown. In the present work, we show that primary thymic epithelial cells (TECs) express glucocorticoid receptors and that high-dosage dexamethasone induces degeneration of the thymic epithelium within 24 h of treatment. Changes in organ morphology are accompanied by a decrease in the TEC transcription factor FoxN1 and its regulator Wnt-4 parallel with upregulation of lamina-associated polypeptide 2 alpha and peroxisome proliferator activator receptor gamma, two characteristic molecular markers for adipose thymic involution. Overexpression of Wnt-4, however, can prevent upregulation of adipose differentiation-related aging markers, suggesting an important role of Wnt-4 in thymic senescence.
Original language | English |
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Pages (from-to) | 241-248 |
Number of pages | 8 |
Journal | Rejuvenation Research |
Volume | 14 |
Issue number | 3 |
DOIs | |
Publication status | Published - 1 Jun 2011 |
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Dive into the research topics of 'Wnt-4 Protects Thymic Epithelial Cells Against Dexamethasone-Induced Senescence'. Together they form a unique fingerprint.Projects
- 1 Finished
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Generation of Intrathymic Microenvironments to Establish T-Cell Tolerance
Anderson, G. (Principal Investigator), Jenkinson, E. (Co-Investigator) & Lane, P. (Co-Investigator)
1/10/10 → 30/09/15
Project: Research Councils