Downregulation of nasal symptoms in patients with allergic rhinitis-Immunological study in mice and human materials-

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To develop treatment methods of patients with allergic rhinitis, we have performed a various immunological experiments, by way of distinguishing induction phase and eliciting phase of type-I allergic reaction in nasal cavity. As results, the following data and conclusions came out from our experiments.1. LPS aggravates nasal symptom, upregulating Th2 cytokine production of mast cells via TLR4.2. IL-15 negatively regulate the allergic symptoms in the effecter phase by inhibition of degranulation of mast cells. IL-15 also negatively regulate the allergic symptoms in the effecter phase by activation of CD8+ T cells. So IL-15 might be useful for a therapeutic approach to control allergic rhinitis with intranasal introduction of it3. Antihistamines with a clinical dosage was able to downregulate the in vitro production of Th2 type cytokines and degranulation from mast cells.4. TLR distribution in nasal epithelial cells were analysed by northern blot analysis and RT-PCR. Respiratory epithelial cells constitutively expressed mRNA for TLR2, 3, 6, but not for TLR4 andTLR9.5. Sublingual immunotherapy has been considered to be a painless and efficacious therapeutic treatment of allergic rhinitis which is known as type-I allergy of nasal mucosa. IL-10 expressing CD^<4+>CD25^+Foxp3^+ Tregs in CLN are involved in the suppression of allergic responses and that CCL19/CCL21 may contribute to it in mice received SLIT.6. Cholera toxin B (CTB) subunit is an efficient mucosal carrier molecule for induction of oral tolerance to antigens and allergens. Feeding mice with rice seed containing CTB-fused T-cell epitopes suppressed allergen-specific IgE responses and pollen-induced clinical symptoms at 50-fold lower doses of T-cell epitopes than required when using control seed.