Decreased FOXP3 protein expression in patients with asthma

Background: T-regulatory cells (T_reg) 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 T_reg, 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⁺CD25^high and CD4 ⁺CD25^highFOXP3⁺ T-cells were similar. However, FOXP3 protein expression within CD4⁺CD25^high T-cells was significantly decreased in asthmatic patients. There was a tendency for increased FOXP3 expression within CD4⁺CD25^high 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⁺CD25^high T_reg. Our findings also suggest that treatment with inhaled glucocorticosteroids in asthmatics might increase this FOXP3 protein expression within the CD4 ⁺CD25^high T-cell population.