| Project/Area Number |
19390434
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Otorhinolaryngology
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| Research Institution | Shimane University |
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Principal Investigator |
KAWAUCHI Hideyuki Shimane University, 医学部, 教授 (50161279)
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| Co-Investigator(Kenkyū-buntansha) |
KATAOKA Shingo 島根大学, 医学部, 講師 (60152667)
SANO Chiaki 島根大学, 医学部, 講師 (70325059)
YAMADA Takaya 島根大学, 総合科学研究支援センター, 准教授 (50191317)
AOI Noriaki 島根大学, 医学部, 助教 (80452556)
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| Project Period (FY) |
2007 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2009: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2008: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2007: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
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| Keywords | アレルギー性鼻炎 / 免疫療法 / 舌下免疫療法 / 調節性T細胞 / Foxp3 / CD4陽性CD25要請制御性T細胞 / CD4陽性CD25陽性制御性T細胞 / Toll-like receptor / 経口免疫療法 / マスト細胞 / IL-15 / Tg mice |
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| Research Abstract |
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 it
3. 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.
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