Dexamethasone suppresses allergic rhinitis and amplifies CD4(+) Foxp3(+) regulatory T cells in vitro

Int Forum Allergy Rhinol. 2015 Oct;5(10):900-6. doi: 10.1002/alr.21579. Epub 2015 Jun 18.

Abstract

Background: Glucocorticosteroids (GCs) are highly effective in mitigating allergic inflammation. In this study, we investigate the effects of dexamethasone (DEX) on regulatory T cells (Tregs) in a murine model of allergic rhinitis (AR).

Methods: BALB/c mice were sensitized to ovalbumin (OVA) followed by intranasal OVA challenge. Mice in the treatment group received DEX by intraperitoneal injection (5 mg/kg/day) 1 hour before the OVA challenge. Further, CD4(+) CD25(-) T cells from the spleens were cultured in presence of DEX. The effects of DEX on CD4(+) Foxp3(+) T cells were then assessed in vivo as well as in vitro.

Results: Frequencies of sneezing and scratching decreased significantly in the DEX-treated group compared to that in the OVA group. Histopathological analyses showed that DEX restored the destroyed and discontinuous ciliated epithelium of the nasal mucosa in the OVA group. Moreover, DEX inhibited the production of interleukin (IL)-4, IL-5, and IL-13 in the nasal cavity lavage fluid in this group. We also observed a significant increase in the percentage of CD4(+) Foxp3(+) T cells in the OVA group. In vivo, DEX treatment significantly decreased the number of CD4(+) Foxp3(+) T cells. However, in vitro, the proportion of these cells increased in the presence of DEX. Furthermore, the number of late stage apoptotic CD4(+) T cells was also significantly increased upon exposure to DEX.

Conclusion: DEX therapy effectively suppresses AR symptoms, but does not result in the expected increase in the frequency of Tregs in vivo. Thus, whether GCs exert immunosuppressive effects by influencing the number of Tregs remains unresolved.

Keywords: allergic rhinitis; glucocorticosteroid; immunoregulation; inflammatory response; regulatory T lymphocyte.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Anti-Inflammatory Agents / adverse effects
  • Apoptosis / drug effects
  • CD4 Antigens / metabolism
  • Cells, Cultured
  • Cytokines / metabolism
  • Dexamethasone / administration & dosage*
  • Dexamethasone / adverse effects
  • Disease Models, Animal
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Nasal Mucosa / drug effects*
  • Nasal Mucosa / immunology
  • Rhinitis, Allergic / drug therapy*
  • Rhinitis, Allergic / immunology
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / immunology

Substances

  • Anti-Inflammatory Agents
  • CD4 Antigens
  • Cytokines
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Dexamethasone