Decreased FOXP3 protein expression in patients with asthma

S. Provoost, T. Maes, Y. M. Van Durme, P. Gevaert, C. Bachert, C. B. Schmidt-Weber, G. G. Brusselle, G. F. Joos, K. G. Tournoy

Research output: Contribution to journalArticlepeer-review

128 Scopus citations

Abstract

Background: T-regulatory cells (Treg) are important in balancing immune responses and maintaining peripheral tolerance. Current evidence suggests that asthma is characterized by a relative deficiency in T reg, allowing T helper 2 cells to expand. In this study, we aimed to evaluate circulating Treg, defined by the protein FOXP3, in both control subjects and patients with stable asthma. Methods: Peripheral blood mononuclear cells (PBMC) of control (n = 14) and asthmatic patients (n = 29) were labeled for CD4, CD25, and intracellular FOXP3 and analyzed using flow cytometry. In CD3/CD28 stimulated PBMC, the effects of dexamethasone on the transcription factors T-bet, GATA-3, FOXP3, and RORc2 and representative cytokines were studied. Results: In control subjects and asthmatic patients, numbers of peripheral blood CD4+CD25high and CD4 +CD25highFOXP3+ T-cells were similar. However, FOXP3 protein expression within CD4+CD25high T-cells was significantly decreased in asthmatic patients. There was a tendency for increased FOXP3 expression within CD4+CD25high T-cells in glucocorticosteroid-treated patients when compared to steroid-naive asthmatic patients. In stimulated PBMC, dexamethasone treatment increased the anti-/proinflammatory transcription ratios of FOXP3/GATA-3, FOXP3/T-bet, and FOXP3/RORc2. Conclusion: Asthmatic patients have decreased FOXP3 protein expression within their CD4+CD25high Treg. Our findings also suggest that treatment with inhaled glucocorticosteroids in asthmatics might increase this FOXP3 protein expression within the CD4 +CD25high T-cell population.

Original languageEnglish
Pages (from-to)1539-1546
Number of pages8
JournalAllergy: European Journal of Allergy and Clinical Immunology
Volume64
Issue number10
DOIs
StatePublished - Sep 2009
Externally publishedYes

Keywords

  • Asthma
  • FOXP3
  • Inhaled corticosteroid treatment
  • T-regulatory cells

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