ワクチンデザイン研究チーム

現代社会では花粉症、喘息、アトピー性皮膚炎、食物アレルギー等、様々なアレルギー疾患の患者数が増加の一途をたどっていますが、未だ有効な根本治療がありません。ワクチンデザイン研究チームは、すべてのアレルギー疾患の原因物質であるIgE抗体の産生量を低下（またはゼロに）させる医薬品を創生していきます。最初に、不変(invariant)ナチュラル・キラーT(iNKT)細胞の免疫制御機能を活性化する低分子化合物、アルファギャルセル誘導体(RCAI-X)を使ったリポソームワクチンの研究開発を進め、実用化を目指します。

研究分野

化学 / 生物学 & 生化学 / 分子生物 & 遺伝学 / 免疫学 / 薬学 & 毒物学 / 臨床医学 / 微生物学

研究テーマ

• iNKT細胞リガンド含有リポソームワクチンによるIgE抗体産生機序の解明
• iNKT細胞リガンド含有リポソームワクチンによる免疫寛容誘導機構の解明
• 新規IgE産生抑制機構の研究

主要論文

1. Shimizu K, Mizuno T, Shinga J, Asakura M, Kakimi K, Ishii Y, Masuda K, Maeda T, Sugahara H, Sato Y, Matsushita H, Nishida K, Hanada KI, Dörrie J, Schaft N, Bickham K, Koike H, Ando T, Nagai R and Fujii SI.:
   "Vaccination with antigen-transfected, NKT cell ligand-loaded, human cells elicits robust in situ immune responses by dendritic cells."
   Cancer Res 73(1):62-73 (2012).
2. Duramad O, Laysang A, Li J, and Ishii Y.:
   "Pharmacologic Expansion of Donor-Derived, Naturally Occurring CD4(+)Foxp3(+) Regulatory T Cells Reduces Acute Graft-versus-Host Disease Lethality Without Abrogating the Graft-versus-Leukemia Effect in Murine Models."
   Biol Blood Marrow Transplant 17(8):1154-1168 (2011).
3. Okayama T, Matsuno Y, Yasuda N, Tsukui T, Suzuta Y, Koyanagi M, Sakaguchi M, Ishii Y, Olivry T, Masuda K.:
   "Establishment of a quantitative ELISA for the measurement of allergen-specific IgE in dogs using anti-IgE antibody cross-reactive to mouse and dog IgE."
   Vet Immunol Immunopathol. 139(2-4):99-106 (2011).
4. Ishii Y, Motohashi S, Shimizu K, Nakayama T, Taniguchi M, and Fujii S.:
   "Application of NKT cells in immunotherapy"
   Curr Immunology Rev, 6, 109-115 (2010).
5. Yasuda N, Masuda K, Tsukui T, Teng A, and Ishii Y.:
   "Identification of canine natural CD3-positive T cells expressing an invariant T-cell receptor alpha chain."
   Vet Immunol Immunopathol. 132(2-4):224-231(2009).
6. Fujita H, Teng A, Nozawa R, Takamoto-Matsui Y, Katagiri-Matsumura H, Ikezawa Z, Ishii Y.:
   "Production of both IL-27 and IFN-{gamma} after the treatment with a ligand for invariant NK T cells is responsible for the suppression of Th2 response and allergic inflammation in a mouse experimental asthma model."
   J Immunol. 183(1):254-260 (2009).
7. Ito T, Hasegawa A, Hosokawa H, Yamashita M, Motohashi S, Naka T, Okamoto Y, Fujita Y, Ishii Y, Taniguchi M, Yano I, Nakayama T.:
   "Human Th1 differentiation induced by lipoarabinomannan/lipomannan from Mycobacterium bovis BCG Tokyo-172."
   Int Immunol. 20(7):849-60 (2008).
8. Ishii Y, Nozawa R, Takamoto-Matsui Y, Teng A, Katagiri-Matsumura H, Nishikawa H, Fujita H, Tamura Y, Taniguchi M.:
   "Alpha-galactosylceramide-driven immunotherapy for allergy"
   Front Biosci. 13:6214-28 (2008).
9. Tamura Y, Teng A, Nozawa R, Takamoto-Matsui Y, Ishii Y.:
   "Characterization of the immature dendritic cells and cytotoxic cells both expanded after activation of invariant NKT cells with alpha-galactosylceramide in vivo."
   Biochem Biophys Res Commun. 369(2):485-92 (2008).
10. Harada M, Magara-Koyanagi K, Watarai H, Nagata Y, Ishii Y, Kojo S, Horiguchi S, Okamoto Y, Nakayama T, Suzuki N, Yeh W-C, Akira S, Kitamura H, Ohara O, Seino K-I, and Taniguchi M.:
    "IL-21–induced Bε cell apoptosis mediated by natural killer T cells suppresses IgE responses."
    J. Exp. Med. 203: 2929-2937 (2006).