Functional analysis of newly identified inducible regulatory T cells in immunological reaction and tolerance

• Project/Area Number: 24390073
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: University of Fukui (2014-2016); Kyoto University (2012-2013)
• Principal Investigator: Sugai Manabu 福井大学, 学術研究院医学系部門, 教授 (90303891)
• Co-Investigator(Kenkyū-buntansha): 黒岡 尚徳 福井大学, 医学部, 准教授 (00293879) ; 森 健太郎 福井大学, 医学部, 助教 (50397296)
• Project Period (FY): 2012-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000); Fiscal Year 2015: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2014: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2013: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2012: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
• Keywords: 慢性炎症 / 自己免疫疾患 / 腫瘍免疫

Outline of Final Research Achievements

Cell fate determination of CD4 T cells (helper T cells) or CD8 T cells (cytotoxic T cells) is occurred in the thymus in a mutually exclusive manner. We found that CD4 T cells differentiate into CD8aa T cells in the periphery in response to transforming growth factor-beta1(TGF-beta1), retinoic acids (RA) and Interleukin-2(IL-2). These cells were designated as CD4-derived CD8aa T cells. We further examined the immuno-regulatory role of CD4-derived CD8aaT cells in various autoimmune models.

Research Products

• [Journal Article] Effects of Usag-1 and Bmp7 deficiencies on murine tooth morphogenesis. (2016)
  • Author(s): Saito K., Takahashi K., Asahara M., Kiso H., Togo Y., Tsukamoto H., Huang B., Sugai M., Shimizu A., Motokawa M., Slavkin HC., Bessho K.
  • Journal Title: BMC Dev Biol. Volume: 16 Issue: 1 Pages: 14-23
  • DOI: 10.1186/s12861-016-0117-x
  • NAID: 120005819500
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Antagonistic Functions of USAG-1 and RUNX2 during Tooth Development. (2016)
  • Author(s): Togo Y., Takahashi K., Saito K., Kiso H., Tsukamoto H., Huang B., Yanagita M., Sugai M., Harada H., Komori T., Shimizu A., MacDougall M., Bessho K.
  • Journal Title: PLoS One Volume: 11 Issue: 8 Pages: e0161067-e0161067
  • DOI: 10.1371/journal.pone.0161067
  • NAID: 120005842696
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Activation of B1a Cells in Peritoneal Cavity by T Cell-Independent Antigen Expressed on Polymeric Micelle (2015)
  • Author(s): Cheol Joo Kim1, Eri Hara2, Akira Shimizu2, Manabu Sugai2 and Shunsaku Kimura1*
  • Journal Title: Journal of Pharmaceutical Sciences Volume: 104 Issue: 5 Pages: 1839-1847
  • DOI: 10.1002/jps.24397
  • Peer Reviewed / Open Access
• [Journal Article] Prospective signs of cleidocranial dysplasia in Cebpb deficiency (2014)
  • Author(s): Boyen Huang1,2, Katsu Takahashi2*, Ernest A Jennings1 , Pongthorn Pumtang-on3 , Honoka Kiso2 , Yumiko Togo2 , Kazuyuki Saito2 , Manabu Sugai4 , Shizuo Akira5 , Akira Shimizu4 and Kazuhisa Bessho2
  • Journal Title: Journal of Biomedical Science Volume: 21 Issue: 1 Pages: 44-48
  • DOI: 10.1186/1423-0127-21-44
  • Peer Reviewed / Open Access
• [Journal Article] Interactions between BMP-7 and USAG-1 (Uterine Sensitization-Associated Gene-1) Regulate Supernumerary Organ Formations (2014)
  • Author(s): Honoka Kiso, Katsu Takahashi , Kazuyuki Saito, Yumiko Togo, Hiroko Tsukamoto, Boyen Huang, Manabu Sugai, Akira Shimizu, Yasuhiko Tabata, Aris N. Economides, Harold C. Slavkin, Kazuhisa Bessho
  • Journal Title: PlosOne Volume: 9 Issue: 5 Pages: 96938-96944
  • DOI: 10.1371/journal.pone.0096938
  • Peer Reviewed / Open Access
• [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] 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 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] T cell independent immune response against “Lactosome” (2014)
  • Author(s): HARA Eri1, KIM Cheol Joo2, SUGAI Manabu1, KIMURA Shunsaku2
  • Organizer: 日本免疫学会
  • Place of Presentation: 京都国際会館
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] B cell-fate determination by mitochondrial ROS via inhibition of heme synthesis (2014)
  • Author(s): Manabu Sugai
  • Organizer: 日本生化学会
  • Place of Presentation: 京都国際会館
  • Year and Date: 2014-10-15 – 2014-10-18
  • Invited
• [Presentation] ミトコンドリアによる活性化B細胞運命決定機構の解析 (2014)
  • Author(s): Kyoung-Jin Jang1, Hiroto Mano1, Koji Aoki2, Tatsunari Hayashi1, Akihiko Muto3,4, Yukiko Nambu1†, Katsu Takahashi5, Katsuhiko Itoh6, Shigeru Taketani7, Stephen L. Nutt8, 9, Kazuhiko Igarashi3,4, Akira Shimizu1, and Manabu Sugai1*
  • Organizer: 日本生化学会
  • Place of Presentation: 京都国際会館
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] Mitochondrial function regulates heme oxygenase-1 expression through modulating ability of heme synthesis (2014)
  • Author(s): Manabu Sugai 1,, Kyoung-Jin Jang 1, Kazuhiko Igarashi2 and Akira Shimizu 1
  • Organizer: 8th Int. Conference on Heme Oxygenases, BioIron & Oxidative Stress
  • Place of Presentation: Sydney(Australia)
  • Year and Date: 2014-10-08 – 2014-10-11
• [Presentation] Essential role of SIP1 and CD19 in B cell differentiation (2013)
  • 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: 千葉
• [Presentation] In situ differentiation of CD8αα Τ cells from CD4 T cells in peripheral lymphoid tissues (2012)
  • Author(s): 南部 由希子、清水 章 、菅井 学 他
  • Organizer: 日本分子生物学会
  • Place of Presentation: 福岡
• [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: 菅井学、清水章、 南部由希子
  • Industrial Property Rights Type: 特許
  • 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: 菅井学、清水章、 南部由希子
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2012-101390
  • Filing Date: 2012-04-16