Allergy Asthma Immunol Res.  2016 May;8(3):264-275. 10.4168/aair.2016.8.3.264.

CpG Oligodeoxynucleotide Inhibits Cockroach-Induced Asthma via Induction of IFN-gamma+ Th1 Cells or Foxp3+ Regulatory T Cells in the Lung

Affiliations
  • 1Department of Life Science, College of Natural Sciences, Hanyang University, Seoul, Korea. jeminchoi@hanyang.ac.kr
  • 2Research Institute for Natural Sciences, Hanyang University, Seoul, Korea.
  • 3Division of Allergy and Immunology, Department of Internal Medicine and Institute of Allergy, Yonsei University College of Medicine, Seoul, Korea. parkjw@yuhs.ac

Abstract

PURPOSE
CpG oligodeoxynucleotide (CpG-ODN), a TLR9 agonist, activates innate immunity and induces Th1 response. Although the immune modulatory effect of CpG-ODN has been extensively studied, its function in cockroach extract-induced allergic asthma has not been studied. Here, we investigated the inhibitory function of CpG-ODN in cockroach extract-induced asthma in mice with different treatment schemes.
METHODS
Scheme 1: BALB/C mice were intra-nasally co-administered by cockroach extract and CpG-ODN twice a week for 3 weeks; Scheme 2: The mice were intra-nasally pre-treated with CpG-ODN at day 0 and cockroach allergen challenge was performed from day 3 as in scheme 1. Scheme 3: Cockroach allergen challenge was performed as in scheme 1 and CpG-ODN was post-treated at day 21. Then, BAL cell count, flow cytometric analysis of alveolar macrophages, regulatory T cells, and lung tissue histology, Th1 and Th2 cytokines, serum IgE, cockroach specific IgE, IgG1/IgG2a ratio, and airway hyper-responsiveness were evaluated.
RESULTS
Mice with repeated intra-nasal exposure to CpG-ODN showed a dramatic decrease in eosinophilic inflammation, goblet cell hyperplasia, and airway hyper-responsiveness with reduction of IL-13, IL-5, and serum IgE, cockroach specific IgE and IgG1/IgG2a ratio. This inhibitory function might be related to the up-regulation of IL-10 and CD4+Foxp3+ regulatory T cells in the lung. Interestingly, one-time challenge of CpG-ODN either prior or posterior to cockroach extract exposure could modulate airway inflammation and hyper-responsiveness via increase of Th1 response.
CONCLUSIONS
Collectively, our data suggest that CpG-ODN treatment modulates Th2 inflammation in the lung by induction of regulatory T cells or Th1 response in a cockroach-induced asthma model.

Keyword

CpG-ODN; cockroach allergen; Th2 inflammation; immune modulation

MeSH Terms

Animals
Asthma*
Cell Count
Cockroaches
Cytokines
Eosinophils
Goblet Cells
Hyperplasia
Immunity, Innate
Immunoglobulin E
Inflammation
Interleukin-10
Interleukin-13
Interleukin-5
Lung*
Macrophages, Alveolar
Mice
T-Lymphocytes, Regulatory*
Th1 Cells*
Up-Regulation
Cytokines
Immunoglobulin E
Interleukin-10
Interleukin-13
Interleukin-5
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