Glucocorticoids upregulate FOXP3 expression and regulatory T cells in asthma
| Autor: | Carsten B. Schmidt-Weber, Kurt Blaser, N. Woolley, Christian Karagiannidis, Pierre-Yves Mantel, G. Hense, Mübeccel Akdis, Cezmi A. Akdis, Beate Rückert, Günther Menz, P. Holopainen |
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| Rok vydání: | 2004 |
| Předmět: |
Adult
CD4-Positive T-Lymphocytes medicine.medical_specialty Regulatory T cell Immunology chemical and pharmacologic phenomena Biology T-Lymphocytes Regulatory Transforming Growth Factor beta1 Interleukin 21 Transforming Growth Factor beta Internal medicine medicine Humans Immunology and Allergy Cytotoxic T cell RNA Messenger IL-2 receptor Promoter Regions Genetic Glucocorticoids FOXP3 Peripheral tolerance Cell Differentiation Forkhead Transcription Factors hemic and immune systems Immunoglobulin E Middle Aged Asthma Interleukin-10 Up-Regulation DNA-Binding Proteins Interleukin 10 medicine.anatomical_structure Endocrinology Gene Expression Regulation Glucocorticoid Microsatellite Repeats medicine.drug |
| Zdroj: | Journal of Allergy and Clinical Immunology. 114:1425-1433 |
| ISSN: | 0091-6749 |
| DOI: | 10.1016/j.jaci.2004.07.014 |
| Popis: | Background T regulatory (T reg ) cells are characterized by expression of suppressive cytokines and the transcription factor FOXP3. They play a key role in balancing immune responses and maintain peripheral tolerance against antigens and allergens. The loss of peripheral tolerance against allergens causes diseases that can be therapeutically controlled with glucocorticoids. Objective The present study investigates whether glucocorticoids affect the activity of T reg cells on the basis of FOXP3 and cytokine expression. Methods CD4 + T cells from healthy donors and glucocorticoid-treated asthmatic patients were isolated, and expression of FOXP3, along with IL-10 and TGF-β1, was determined. The effect of glucocorticoids on T reg cells was measured in vivo before and after GC treatment and in in vitro cultures. Results FOXP3 mRNA expression was significantly increased in asthmatic patients receiving inhaled glucocorticoid treatment, systemic glucocorticoid treatment, or both. FOXP3 tightly correlated with IL10 mRNA expression. No correlation of FOXP3 mRNA expression was observed in relation to a (GT)n microsatellite promoter polymorphism on chromosome Xp11.23 or total IgE level. The frequency of CD25 + memory CD4 + T cells and transient FOXP3 mRNA expression by CD4 + T cells significantly increased after systemic glucocorticoid treatment, whereas TGFB1 expression did not change. Furthermore, glucocorticoids induced IL10 and FOXP3 expression in short-term and long-term cultures in vitro . Conclusion These findings demonstrate that glucocorticoid treatment is not only immunosuppressive and anti-inflammatory but also promotes or initiates differentiation toward T R 1 cells by a FOXP3-dependent mechanism. Strategies that convert transient glucocorticoid-induced T reg activity into a stable phenotype might improve allergy and asthma therapy. |
| Databáze: | OpenAIRE |
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