Wnt-4 protects thymic epithelial cells against dexamethasone-induced senescence

Talaber, Gergely and Kvell, Krisztian and Varecza, Z. and Boldizsár, Ferenc and Parnell, Sonia and Jenkinson, Eric J. and Anderson, Graham and Berki, Tímea and Pongracz, Judit (2011) Wnt-4 protects thymic epithelial cells against dexamethasone-induced senescence. Rejuvenation Research, 14 (3). pp. 241-248. ISSN 1549-1684

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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 2α and peroxisome proliferator activator receptor γ, 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.

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