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

为探索变应性鼻炎的治疗方法，我们进行了多种免疫学实验，区分鼻腔I型变态反应的诱导期和诱发期。根据实验结果，得出了以下数据和结论。脂多糖加重鼻部症状，通过TLR4.2上调肥大细胞Th2细胞因子的产生。IL-15通过抑制肥大细胞脱颗粒，在效应期对过敏症状进行负性调节。IL-15还通过激活CD8+T细胞在效应期对过敏症状进行负性调节。因此，IL-15可能是一种通过鼻腔注射来控制变应性鼻炎的治疗方法。临床剂量的抗组胺药物能抑制体外Th2型细胞因子的产生和肥大细胞脱颗粒。用Northern印迹分析和RT-PCR分析TLR在鼻黏膜上皮细胞中的分布。呼吸道上皮细胞表达TLR2、3、6，但不表达TLR4和TLR9.5。舌下免疫疗法被认为是治疗变应性鼻炎的一种无痛且有效的治疗方法。变应性鼻炎被称为鼻黏膜I型变态反应。CLN中表达CD25+Foxp3^+Tregs的IL-10参与了SLIT小鼠过敏反应的抑制，CCL19/CCL21可能参与了SLIT小鼠的过敏性反应。霍乱毒素B亚单位(CTB)是一种有效的黏膜载体分子，可诱导机体对抗原和过敏原的耐受。用含有CTB融合T细胞表位的大米种子喂养小鼠，可以抑制过敏原特异性IgE反应和花粉引起的临床症状，而T细胞表位的剂量比使用对照种子时所需的剂量低50倍。

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.