Decreased FOXP3 protein expression in patients with asthma

Allergy. 2009 Oct;64(10):1539-46. doi: 10.1111/j.1398-9995.2009.02056.x. Epub 2009 Apr 9.

Abstract

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(high)FOXP3(+) 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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Asthmatic Agents / pharmacology
  • Anti-Asthmatic Agents / therapeutic use
  • Asthma / drug therapy
  • Asthma / genetics
  • Asthma / immunology
  • Asthma / metabolism
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Dexamethasone* / pharmacology
  • Dexamethasone* / therapeutic use
  • Down-Regulation* / drug effects
  • Female
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism*
  • Gene Expression Regulation / drug effects
  • Glucocorticoids* / pharmacology
  • Glucocorticoids* / therapeutic use
  • Humans
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • Treatment Outcome

Substances

  • Anti-Asthmatic Agents
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Glucocorticoids
  • IL2RA protein, human
  • Interleukin-2 Receptor alpha Subunit
  • Dexamethasone