Development of Airway Allergic Diseases and Immunotherapy in Children / 대한이비인후과학회지

Allergic march is a part of a phase that occurs in a series of continuous steps in disease of pediatric patients, which proceeds from atopic dermatitis to asthma, and from asthma to allergic rhinitis. Recently, several hypotheses have been raised to explain the allergic march. Among them, the study of the hygiene theory related to microbiota, and the study on the role of innate cytokines which occurs in skin barrier damage are attracting attentions. If the interaction between the microbiota and the immune system occurs improperly, the activity of the regulatory T cell becomes insufficient and the immune-regulatory function is reduced, resulting in allergic diseases. Because of the skin barrier disruption, the innate cytokines are activated, thus resulting in Th2 inflammation reaction being increased. Considering this pathogenesis, blocking the linkage to pathogens is regarded to play an important role in preventing and treating allergic march.

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

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.