Development of new therapies for tumor and autoimmunity using CD8aaT cells

• Project/Area Number: 24659148
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Pathological medical chemistry
• Research Institution: Kyoto University
• Principal Investigator: SUGAI Manabu 京都大学, 医学(系)研究科(研究院), 講師 (90303891)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 自己免疫疾患 / 制御性T細胞 / 腫瘍免疫

Research Abstract

Cell fate determination of helper T cells (CD4 T cells) or cytotoxic T cells (CD8 T cells) is mutually exclusive process depending on antigen recognition, which occurs in the thymus. We found that retinoic acid and transforming growth factor-b1 promoted the differentiation of CD8 aaT cells from CD4 T cells in peripheral lymphoid tissues. And we examined the expression patterns of various genes in differentiated CD8aa T cells and compared with those in iTreg cells. Furthermore, we found various compounds, which regulate differentiation of CD8aa T cells from CD4 cells.

Research Products

• [Journal Article] Functional Evaluation of Activation-dependent Alterations in the Sialoglycan Composition of T Cells (2014)
  • Author(s): Naito-Matsui, Y., Takada, S., Kano, Y., Iyoda, T., Sugai, M., Shimizu, A., Inaba, K., Nitschke, L., Tsubata, T., Oka, S., Kozutsumi, Y. and Takematsu, H.
  • Journal Title: J . Biol. Chem. Volume: 289 Pages: 1564-1579
• [Journal Article] Functional evaluation of activation-dependent alterations in the sialoglycan composition of T cells. (2014)
  • Author(s): Naito-Matsui Y, Takada S, Kano Y, Iyoda T, Sugai M, Shimizu A, Inaba K, Nitschke L, Tsubata T, Oka S, Kozutsumi Y, and Takematsu H.
  • Journal Title: J. Biol. Chem. Volume: 289 Issue: 3 Pages: 1564-1579
  • DOI: 10.1074/jbc.m113.523753
  • Peer Reviewed / Open Access
• [Journal Article] Phenotypes of CCAAT/enhancer-binding protein beta deficiency : hyperdontia (2013)
  • Author(s): Huang, B., Takahashi, K., Sakata-Goto, T., Kiso, H., Togo, Y., Saito, K., Tsukamoto, H., Sugai, M., Shimizu, A. and Bessho, K.
  • Journal Title: Oral Diseases Volume: 19
• [Journal Article] The metalloid arsenite induces nuclear export of Id3 possibly via binding to the N-terminal cysteine residues (2013)
  • Author(s): Kurooka, H., Sugai, M., Mori, K. and Yokota, Y.
  • Journal Title: Biochem.Biophys. Res. Commun. Volume: 433
• [Journal Article] Evasion from accelerated blood clearance of nanocarrier named as"Lactosome" (2013)
  • Author(s): Hara, E., Makino, A., Kurihara, K., Sugai, M.,Shimizu, A., Hara, I., Ozeki, E., Kimura, S.
  • Journal Title: Biochim. Biophys. Acta Volume: 1830
• [Journal Article] Evasion from accelerated blood clearance of nanocarrier named as "Lactosome" induced by excessive administration of Lactosome. (2013)
  • Author(s): Hara, E., Makino, A., Kurihara, K., Sugai, M., Shimizu, A., Hara, I., Ozeki, E. and Kimura, S.
  • Journal Title: Biochem. Biophys. Acta-General Sub. Volume: 1830 Issue: 8 Pages: 4046-4052
  • DOI: 10.1016/j.bbagen.2013.03.024
  • Peer Reviewed
• [Journal Article] The metalloid arsenite induces nuclear export of Id3 possibly via binding to the N-terminal cysteine residues (2013)
  • Author(s): Kurooka, H., Sugai, M., Mori, K. and Yokota, Y.
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 433 Issue: 4 Pages: 579-585
  • DOI: 10.1016/j.bbrc.2013.03.027
  • Peer Reviewed
• [Journal Article] Phenotypes of CCAAT/enhancer-binding protein beta deficiency: Hyperdontia and elongated coronoid process. (2013)
  • Author(s): Huang, B., Takahashi, K., Sakata-Goto, T., Kiso, H., Togo, Y., Saito, K., Tsukamoto, H., Sugai, M., Akira, S., Shimizu, A. and Bessho, K.
  • Journal Title: Oral Diseases Volume: 19 Issue: 2 Pages: 144-150
  • DOI: 10.1111/j.1601-0825.2012.01963.x
  • Peer Reviewed
• [Journal Article] In situ differentiation of CD8ααT cells from CD4 T cells in peripheral lymphoid tissues (2012)
  • Author(s): Nambu, Y., Hayashi, T., Jang, KJ., Aoki, K., Mano, H., Nakano, K., Osato, M., Takahashi, K., Itoh, K., Teramukai, S., Komori, T.,Fujita, J., Ito, Y., Shimizu, A. & Sugai, M.
  • Journal Title: Scientific Reports Volume: 2 Pages: 645-623
• [Journal Article] Id2 controls chondrogenesis acting downstream of BMP signaling during maxillary morphogenesis (2012)
  • Author(s): Sakata-Goto, T., Takahashi, K., Kiso, H., Huang, B., Tsukamoto, H., Takemoto, M., Hayashi, T., Sugai, M., Nakamura, T., Tokota, Y., Shimizu, A., Slavkin, H. and Bessho, K.
  • Journal Title: Bone Volume: 50 Pages: 69-78
• [Journal Article] 制御性T細胞と大腸炎関連派発癌GI (2012)
  • Author(s): 菅井学、南部由希子、清水章
  • Journal Title: Research Volume: 20(6) Pages: 466-471
• [Journal Article] In situ differentiation of CD8αα T cells from CD4 T cells in peripheral lymphoid tissues (2012)
  • Author(s): Nambu Y., Hayashi T., Jang KJ, Aoki K., Mano H., Nakano K., Osato M., Takabashi K., Itoh K., Teramukai S., Komon T., Fujita J., Ito Y., Shimizu
  • Journal Title: Scientific Reports Volume: 2 Issue: 1 Pages: 930-930
  • DOI: 10.1038/srep00642
  • Peer Reviewed
• [Journal Article] Id2 controls chondrogenesis acting downstream of BMP signaling during maxillary morphogenesis (2012)
  • Author(s): Sakata-Goto T
  • Journal Title: Bone Volume: 50 Issue: 1 Pages: 69-78
  • DOI: 10.1016/j.bone.2011.09.049
  • Peer Reviewed
• [Presentation] Essential role of SIP1 and CD19 in B cell differentiation (2013)
  • Author(s): Hayashi T, Nambu Y, Jang KJ, Mano H, Higashi Y, Kristin V, Danny H, Shimizu A, Sugai M
  • Organizer: 日本免疫学会学術集会
  • Place of Presentation: 横浜
• [Presentation] Essential role of SIP1 and CD19 in B cell differentiation (2012)
  • Author(s): Hayashi T, Nambu Y, Jang KJ, Mano H, Higashi Y, Kristin V, Danny H, Shimizu A, Sugai M
  • Organizer: 日本免疫学会学術集会
  • Place of Presentation: 神戸
• [Presentation] In situ differentiation of CD8aa T cells from CD4 Tcells in peripheral lymphoid tissues (2012)
  • Author(s): Nambu Y, Hayashi T, Jang KJ, Aoki K, Mano H, Nakano K, Osato M, Takahashi K, Itoh K, Teramukai S, Komori T, Fujita J, Ito Y, Shimizu A, Sugai M
  • Organizer: 日本分子生物学会年会
  • Place of Presentation: 福岡
• [Presentation] In situ differentiation of CD8αα Τ cells from CD4 T cells in peripheral lymphoid tissues (2012)
  • Author(s): 南部 由希子、林 達成、Kyoung-Jin Jang、青木 耕史、眞野浩人、中野圭子、大里 元美、髙橋 克、 伊藤 克彦、手良向 聡、小守 壽文、藤田 潤、伊藤 嘉明、清水 章 、菅井 学
  • Organizer: 日本分子生物学会
  • Place of Presentation: 福岡
• [Presentation] Essential role of SIP1 and CD19 in B cell differentiation
  • Author(s): HAYASHI T., NAMBU Y., MANO H., HIGASHI Y., Kristin V., Danny H., SHIMIZU A. and SUGAI M.
  • Organizer: 日本免疫学会
  • Place of Presentation: 幕張メッセ
• [Patent(Industrial Property Rights)] T細胞の分化誘導方法、T細胞の製造方法、T細胞、医薬組成物、及び、スクリーニング方法 (2013)
  • Inventor(s): 菅井学、清水章、南部由希子
  • Industrial Property Rights Holder: 京都大学
  • Filing Date: 2013-03-12
  • Overseas
• [Patent(Industrial Property Rights)] T細胞の分化誘導方法、T細胞の製造方法、T細胞、医薬組成物、及び、スクリーニング方法 (2012)
  • Inventor(s): 菅井学、清水章、南部由希子
  • Industrial Property Rights Holder: 京都大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2012-04-26
• [Patent(Industrial Property Rights)] T細胞の分化誘導方法、T細胞の製造方法、T細胞、医薬組成物、及び、スクリーニング方法 (2012)
  • Inventor(s): 菅井学、清水章、南部由希子
  • Industrial Property Rights Holder: 菅井学、清水章、南部由希子
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2012-101390
  • Filing Date: 2012-04-26