title: Wnt-4 protects thymic epithelial cells against dexamethasone-induced senescence.
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.
authors: Department of Immunology and Biotechnology, University of Pecs, Faculty of Medicine, Pecs, Hungary.
authors: Gergely
authors: G
authors: Talaber
authors: Krisztian
authors: K
authors: Kvell
authors: Zoltan
authors: Z
authors: Varecza
authors: Ferenc
authors: F
authors: Boldizsar
authors: Sonia M
authors: SM
authors: Parnell
authors: Eric J
authors: EJ
authors: Jenkinson
authors: Graham
authors: G
authors: Anderson
authors: Timea
authors: T
authors: Berki
authors: Judit E
authors: JE
authors: Pongracz
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects; D000818:Animals; D002460:Cell Line; D054338:Cell Transdifferentiation / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects*; D019610:Cytoprotection / Q000187:drug effects*; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology*; D060528:Wnt4 Protein / Q000378:metabolism*
chemical_list: D011965:Receptors, Glucocorticoid; D060528:Wnt4 Protein; D003907:Dexamethasone