Molecular mechanisms of sublingual immunotherapy

• Project/Area Number: 20590502
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: Tokyo Metropolitan Organization for Medical Research
• Principal Investigator: HIROI Takachika Tokyo Metropolitan Organization for Medical Research, 東京都臨床医学総合研究所, 副参事研究員 (80228824)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 粘膜免疫 / 舌下免疫療法 / スギ花粉症 / アレルギー / IgE / 免疫寛容 / T細胞 / 抗原提示細胞 / 脱顆粒 / 舌下減感作療法 / Th2 / IL-4 / OVA

Research Abstract

In this study, we comparatively examined the effect of SLIT on antigen-induced airway inflammation developed in bronchoalveolar and nasal cavities in mice. Massive infiltration of eosinophils as well as neutrophils into the bronchoalveolar cavity was induced by intratracheal OVA challenge. In the nasal cavity, eosinophil accumulation was occurred, though the number of neutrophils was not significantly changed, in response to nasal antigen challenge. These antigen-induced airway inflammatory responses, including increase in the number of eosinophils and/or neutrophils in the bronchoalveolar and nasal cavities were clearly suppressed by sublingual OVA administration. This animal model displaying differential inflammatory responses in the bronchoalveolar and nasal cavities may be useful to elucidate the efficacy and mechanisms of SLIT against various allergic diseases.

Research Products

• [Journal Article] Prevention of allergic asthma by vaccination with transgenic rice-seed expressing mite allergen : induction of allergen-specific oral tolerance without bystander suppression. (2011)
  • Author(s): Suzuki, K., Kaminuma, O., Yang, L., Takai, T., Mori, A., Umezu-Goto, M., Ohtomo, T., Ohmachi, Y., Noda, Y., Hirose, S., Okumura, K., Ogawa, H., Takada, K., Hirasawa, M., Hiroi, T., Takaiwa, F.
  • Journal Title: Plant Biothecnol J. Volume: In press
  • Peer Reviewed
• [Journal Article] Rice seed ER-derived protein body as an efficient delivery vehicle for oral tolerogenic peptides. (2010)
  • Author(s): Takagi, H., Hiroi, T., Hirose, S., Yang, L., Takaiwa, F.
  • Journal Title: Peptides. Volume: 31 Pages: 1421-1425
  • Peer Reviewed
• [Journal Article] Selective down-regulation of Th2 cytokines by C-terminal binding protein 2 in human T cells. (2010)
  • Author(s): Kitamura, F., Kitamura, N., Mori, A., Tatsumi, H., Nemoto, S., Miyoshi, H., Miyatake, S., Hiroi, T., Kaminuma, O.
  • Journal Title: Int Arch Allergy Imunol. Volume: 152 Pages: 18-21
  • Peer Reviewed
• [Journal Article] Antibody-mediated blockade of IL-15 signaling reverses autoimmune intestinal damage in a mouse model of celiac disease (2009)
  • Author(s): Yokoyama S., Watanabe N., Sato N., Filkoski L., Tanaka T., Miyasaka M. , Waldmann T.A., Hiroi T., Perera, P.L.
  • Journal Title: Proc. Natl Acad Sci USA 106 Pages: 15849-54
• [Journal Article] T. T-box 21 transcription factor is responsible for distorted TH2 differentiation in human peripheral CD4+ T cells (2009)
  • Author(s): Kaminuma O., Kitamura F., Miyatake S., Yamaoka K., Miyoshi H, Inokuma S, Tatsumi H, Nemoto S, Kitamura N, Mori A, Hiroi
  • Journal Title: J Allergy Clin Immunol 123 Pages: 813-823
• [Journal Article] Suppressive role of C-terminal binding protein 1 in IL-4 synthesis in human T cells (2009)
  • Author(s): Kitamura N., Motoi Y., Mori A., Tatsumi H., Nemoto S., Miyoshi H., Kitamura F., Miyatake S., Hiroi T., Kaminuma O.
  • Journal Title: Biochem Biophys Res Commun 382 Pages: 326-330
• [Journal Article] Antibody-mediated blockade of IL-15 signaling reverses autoimmune intestinal damage in a mouse model of celiac disease (2009)
  • Author(s): Yokoyama, S., Watanabe, N., Sato, N., Filkoski, L., Tanaka, T., Miyasaka, M., Waldmann, T.A., Hiroi, T., Perera, P.L.
  • Journal Title: Proc.Natl Acad Sci USA 106 Pages: 15849-15854
  • Peer Reviewed
• [Journal Article] T-box 21 transcription factor is responsible for distorted TH2 differentiation in human peripheral CD4^+ T cells (2009)
  • Author(s): Kaminuma, O., Kitamura, F., Miyatake, S., Yamaoka, K., Miyoshi H, Inokuma S, Tatsumi H, Nemoto S, Kitamura N, Mori A, Hiroi, T.
  • Journal Title: J Allergy Clin Immunol 123 Pages: 813-823
  • Peer Reviewed
• [Journal Article] Development of transgenic rice expressing mite antigen for a new concept of immunotherapy (2009)
  • Author(s): Suzuki, K., Kaminuma, O., Yang, L., Motoi, Y., Takai, T., Ichikawa, S., Okumura, K., Ogawa, H., Mori, A., Takaiwa, F., Hiroi, T.
  • Journal Title: Int Arch Allergy Immunol 149 Pages: 21-24
  • Peer Reviewed
• [Journal Article] T-bet is responsible for incomplete Th2 differentiation in human peripheral CD4+ T cells (2009)
  • Author(s): Kaminuma, O., Kitamura, F., Miyatake, S., Miyoshi, H., Miyawaki, A., Inokuma, S., Tatsumi, H., Kitamura, N., Mori, A., Hiroi, T.
  • Journal Title: J Allergy Clin Immunol (In press)
  • Peer Reviewed
• [Journal Article] Antibody-mediated blockade of IL-15 signaling reverses autoimmune intestinal damage in transgenic mouse model of celiac disease (2009)
  • Author(s): Yokoyama, S., Watanabe, N., Sato, N., Filkoski, L., Tanaka, T., Miyasaka, M., Waldmann, TA., Hiroi, T. (corresponding author), Perera, LP.
  • Journal Title: Proc. Natl. Acad. Sci. USA (In press)
  • Peer Reviewed
• [Journal Article] Efficient induction of oral tolerance by fusing cholera toxin B subunit with allergen-specific T-cell epitopes accumulated in rice seed (2008)
  • Author(s): Takagi, H., Hiroi, H., Yang, L., Takamura, K., Ishimitsu, R., Kawauchi, H., Takaiwa, F.
  • Journal Title: Vaccine 26 Pages: 6027-6030
  • Peer Reviewed
• [Presentation] スギ花粉症舌下免疫療法における治療効果を予測するバイオマーカーの検索 (2011)
  • Author(s): 廣井隆親
  • Organizer: 日本耳鼻科学会免疫アレルギー
  • Place of Presentation: 大分(招待講演)
  • Year and Date: 2011-02-12
• [Presentation] ZFPM1/CtBP1コンプレックスはGATA-3によるTh2分化を抑制する (2010)
  • Author(s): 神沼修,北村紀子,森晶夫,巽英樹,根本荘一,廣井隆親
  • Organizer: 第60回日本アレルギー学会総会
  • Place of Presentation: 東京
  • Year and Date: 2010-11-26
• [Presentation] Differential contribution of CCR4 expressed on Th2 and Th17 cells to antigen-induced airway inflammation (2010)
  • Author(s): Kaminuma O, Kitamura F, Motoi Y, Suzuki K, Katayama K, Hiroi T, Ohtomo T, Mori A, Nagakubo D, Hieshima K, Yoshie O.
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: Kobe
  • Year and Date: 2010-08-24
• [Presentation] Hyperexpression of T-bet is responsible for incomplete human Th2 differentiation (2009)
  • Author(s): Kaminuma, O., Kitamura, N., Mori, A., Tatsumi, H., Nemoto, S., Inokuma, S., Miyoshi, H., Kitamura, F., Miyatake, S., Yamaoka, K., Hiroi, T
  • Organizer: 第39回日本免疫学会総会
  • Place of Presentation: 大阪府・大阪国際会議場
  • Year and Date: 2009-12-03
• [Presentation] Hyperexpression of T-bet is responsible for incomplete human Th2 differentiation (2009)
  • Author(s): Kaminuma O., Kitamura N., Mori A., Tatsumi H., Nemoto S., Inokuma S., Miyoshi H., Kitamura F., Miyatake S., Yamaoka K., Hiroi T.
  • Organizer: 第39回日本免疫学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-02
• [Presentation] T細胞依存性の好酸球性気道炎症に対するCCR4拮抗薬の作用 (2009)
  • Author(s): 神沼修、大友隆之、森晶夫、長久保大輔、稗島州雄、義江修、鈴木一矢、廣井隆親
  • Organizer: 第59回日本アレルギー学会秋季学術大会
  • Place of Presentation: 秋田
  • Year and Date: 2009-10-29
• [Presentation] ヒトT細胞のIL-4産生に対するC-terminal binding proteinの役割 (2009)
  • Author(s): 神沼修、北村紀子、本井祐二、北村ふじ子、宮武昌一郎、三好浩之、巽英樹、根本荘一、森晶夫、廣井隆親
  • Organizer: アレルギー・好酸球研究会2009
  • Place of Presentation: 東京
  • Year and Date: 2009-06-20
• [Presentation] マウスを用いた舌下免疫療法モデル実験系の開発 (2009)
  • Author(s): 鈴木一矢、神沼修、森晶夫、廣井隆親
  • Organizer: アレルギー・好酸球研究会2009
  • Place of Presentation: 東京
  • Year and Date: 2009-06-20
• [Presentation] T細胞依存性のアレルギー性炎症発症におけるCD44の役割 (2008)
  • Author(s): 神沼修, 加藤茂樹, 大友隆之, 森晶夫, 廣井隆親
  • Organizer: 第58回日本アレルギー学会総会
  • Place of Presentation: 東京
• [Presentation] C-terminal transactivation domain is required for NFAT-mediated TNF-alpha synthesis by T cells (2008)
  • Author(s): Kaminuma, O., Kitamura, F., Kitamura, N., Miyatake, S., Hiroi T
  • Organizer: 第38回日本免疫学会総会
  • Place of Presentation: 京都
• [Presentation] Prevention of allergen-induced airway inflammation by Der p 1 expressed transgenic rice (2008)
  • Author(s): Suzuki, K., Lijun, Y., Takai, T., Ichikawa, S., Hirose, S., Mori, A., Umezu-Goto, M., Ohmachi, Y., Noda, Y., Okumura, K., Ogawa, H., Takada, K., Hirasawa, M., Kaminuma, O., Takaiwa, F., Hiroi, T.
  • Organizer: 第38回日本免疫学会総会
  • Place of Presentation: 京都
• [Book] 舌下免疫療法の治療効果を予測するシステムを構築 (2010)
  • Author(s): 廣井隆親
  • Publisher: Medical Tribune special Issue
• [Book] 免疫療法:スギ花粉症舌下免疫療法の治療効果に関わるバイオマーカーの検索 (2010)
  • Author(s): 渡邊伸昌、神沼修、廣井隆親
  • Publisher: アレルギー免疫
• [Remarks] ホームページ等
  • URL: http://www.igakuken.or.jp/
• [Remarks]
  • URL: http://www.rinshoken.or.jp/AI/
• [Remarks]
  • URL: http://www.rinshoken.or.jp/AI/
• [Remarks]
  • URL: http://www.rinshoken.or.jp/AI/
• [Patent(Industrial Property Rights)] 減感作療法における治療効果を予測するバイオマーカー (2010)
  • Inventor(s): 廣井隆親、大久保公裕
  • Industrial Property Rights Holder: 東京都医学研究機構
  • Filing Date: 2010-10-25
• [Patent(Industrial Property Rights)] 減感作療法における治療効果を予測するバイオマーカー (2010)
  • Inventor(s): 廣井隆親
  • Industrial Property Rights Holder: 財団法人東京都医学研究機構
  • Filing Date: 2010-10-25
  • Overseas
• [Patent(Industrial Property Rights)] 減感作療法における治療効果を予測するバイオマーカー (2009)
  • Inventor(s): 廣井隆親
  • Industrial Property Rights Holder: 財団法人東京都医学研究機構
  • Filing Date: 2009-10-20