CpG Oligodeoxynucleotide Inhibits Cockroach-Induced Asthma via Induction of IFN-gamma+ Th1 Cells or Foxp3+ Regulatory T Cells in the Lung.
10.4168/aair.2016.8.3.264
- Author:
Do Hyun KIM
1
;
Jung Ho SOHN
;
Hong Jai PARK
;
Jae Hyun LEE
;
Jung Won PARK
;
Je Min CHOI
Author Information
1. Department of Life Science, College of Natural Sciences, Hanyang University, Seoul, Korea. jeminchoi@hanyang.ac.kr
- Publication Type:Original Article
- Keywords:
CpG-ODN;
cockroach allergen;
Th2 inflammation;
immune modulation
- MeSH:
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
- From:Allergy, Asthma & Immunology Research
2016;8(3):264-275
- CountryRepublic of Korea
- Language:English
-
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.
