title: CpG Oligodeoxynucleotide Inhibits Cockroach-Induced Asthma via Induction of IFN-γ⁺ Th1 Cells or Foxp3⁺ Regulatory T Cells in the Lung.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Life Science, College of Natural Sciences, Hanyang University, Seoul, Korea.|Research Institute for Natural Sciences, Hanyang University, Seoul, Korea.
authors.forename: Do Hyun
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Life Science, College of Natural Sciences, Hanyang University, Seoul, Korea.|Research Institute for Natural Sciences, Hanyang University, Seoul, Korea.|Division of Allergy and Immunology, Department of Internal Medicine and Institute of Allergy, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jung Ho
authors.initials: JH
authors.lastname: Sohn
authors.affiliation: Department of Life Science, College of Natural Sciences, Hanyang University, Seoul, Korea.|Research Institute for Natural Sciences, Hanyang University, Seoul, Korea.
authors.forename: Hong Jai
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine and Institute of Allergy, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jae Hyun
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine and Institute of Allergy, Yonsei University College of Medicine, Seoul, Korea. parkjw@yuhs.ac.
authors.forename: Jung Won
authors.initials: JW
authors.lastname: Park
authors.affiliation: Department of Life Science, College of Natural Sciences, Hanyang University, Seoul, Korea.|Research Institute for Natural Sciences, Hanyang University, Seoul, Korea. jeminchoi@hanyang.ac.kr.
authors.forename: Je Min
authors.initials: JM
authors.lastname: Choi
keywords: CpG-ODN; Th2 inflammation; cockroach allergen; immune modulation