Molecular mechanism of T cell development in Notch signal mediated nitch

• Project/Area Number: 21390154
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: Juntendo University
• Principal Investigator: HABU Sonoko 順天堂大学, 医学部, 客員教授 (30051618)
• Co-Investigator(Kenkyū-buntansha): MAEDA Keiko 順天堂大学, 大学院・医学研究科, 助教 (20053374) ; SATAKE Masanobu 東北大学, 加齢医学研究所, 教授 (50178688)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000); Fiscal Year 2011: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2010: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2009: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
• Keywords: 免疫学 / 胸腺ノッチ / T細胞分化 / ノッチシグナル

Research Abstract

In this study, we showed that in theT cell developing pathway, GATA3 and Runx1, T cell specific transcription factors, are induced to express correlatively to Notch receptor on immature T cell in the thymus. Notch ligand required for T cells development is also characterized. The over-expression of these transcription factors impaired the early stage developing pathway. Collectively, developing stage specific Notch signaling is suggested regulate the expression of both transcription factors. We also established human Notch L transgenic mice.

Research Products

• [Journal Article] Runx1 deficiency in CD4+T cells causes fatal autoimmune inflammatory lung disease due to spontaneous hyperactivation of cells (2012)
  • Author(s): Wong WF, Kohu K, Nakamura A, Ebina M, Kikuchi T, Tazawa R, Tanaka K, Kon S, Funaki T, Sugahara-Tobinai R, Looi CY, Endo S, Funayama R, Kurokawa M, Habu S, Ishii N, Fukumoto M, Nakata K, Takai T, and Satake M
  • Journal Title: J Immunol Volume: 188 Pages: 5408-5420
  • Peer Reviewed
• [Journal Article] GATA-3 regulates contact hyperresponsiveness in a murine model of allergic dermatitis (2012)
  • Author(s): Tama uchi H, Amoh Y, Itoh M, Terashima M, Masuzawa M, Habu S, Katsuoka K and Iwabuchi K
  • Journal Title: Immunobiology Volume: 217 Pages: 446-454
  • Peer Reviewed
• [Journal Article] Critical role of transcription factor PU. 1 in the expression of CD80 and CD86 on dendritic cells (2011)
  • Author(s): Kanada S, Nishiyama C, Nakano N, Suzuki R, Maeda K, Hara M, Kitamura N, Ogawa H, Okumura K
  • Journal Title: Blood Volume: 117 Pages: 2211-2222
  • Peer Reviewed
• [Journal Article] Naive CD4+ T cells of Peyer's patches produce more IL-6 than those of spleen in response to antigenic stimulation (2011)
  • Author(s): Hashiguchi M, et al
  • Journal Title: Immunol Lett Volume: 141 Pages: 109-115
  • Peer Reviewed
• [Journal Article] Antitumor effect of new HER2 peptide vaccination based on B cell epitope (2011)
  • Author(s): Miyako H, et al
  • Journal Title: Anticancer Research Volume: 31 Pages: 3361-3368
  • Peer Reviewed
• [Journal Article] IL-10 controls Th2-type cytokine production and eosinophil infiltration in a mouse model of allergic airway inflammation (2011)
  • Author(s): Kosaka S, et al
  • Journal Title: Immunobiology Volume: 31 Pages: 3361-3367
  • Peer Reviewed
• [Journal Article] Over-expression of Runxtranscription factor impairs the development of thymocytes from the double-negative to double-positive stages (2010)
  • Author(s): Wong WF, Nakazato M, Watanabe T, Kohu K, Ogata T, Yoshida N, Sotomaru Y, Ito M, Araki K, Telfer J, Fukumoto M, Suzuki D, Sato T, Hozumi K, Habu S, Satake M
  • Journal Title: Immunology Volume: 130 Pages: 243-253
  • Peer Reviewed
• [Journal Article] Notch ligands transduce different magnitudes of signaling critical for determination of T cell fate (2010)
  • Author(s): Abe N, Hosumi K, Yagita H and Habu S
  • Journal Title: Eur J Immunol Volume: 40 Pages: 2608-2617
  • Peer Reviewed
• [Journal Article] IL-10 controls Th2-type cytokine production and eosinophil infiltration in a mouse model of allergic airway inflammation (2010)
  • Author(s): Kosa ka S, Tamauchi H, Terashima M, Maruyama H, Habu S, Kitasato H
  • Journal Title: Immunobiology Volume: 216 Pages: 811-820
  • Peer Reviewed
• [Journal Article] Th2 Immune Response Plays a Critical Role in the Development of Nickel-Induced Allergic Contact Dermatitis (2010)
  • Author(s): Matsumura Y, Kanoh M, Habu S, Komotori J, Niiyama S, Tamauchi H, Amoh Y, Terashima M, Katsuoka K
  • Journal Title: Allergy Immunol Volume: 153 Pages: 303-314
  • Peer Reviewed
• [Journal Article] GATA2 and Sp1 positively regulate the c-kit promoter in mast cells (2010)
  • Author(s): Maeda K, Nishiyama C, Ogawa H, Okumura K
  • Journal Title: J Immunol Volume: 185 Pages: 4252-4260
  • Peer Reviewed
• [Journal Article] Notch ligands transduce different magnitudes of signaling critical for determination of T-cell fate. (2010)
  • Author(s): Abe N
  • Journal Title: Eur J Immunol Volume: 40 Pages: 2608-17
  • Peer Reviewed
• [Journal Article] Th2 immune response plays a critical role in the development of nickel-induced allergic contact dermatitis (2010)
  • Author(s): Niiyama S
  • Journal Title: Int Arch Allergy Immunol Volume: 153 Pages: 303-14
  • Peer Reviewed
• [Journal Article] Over-expression of Runx1 transcription factor impairs the development of thymocytes from the double-negative to double-positive stages. (2010)
  • Author(s): Wong WF
  • Journal Title: Immunology Volume: 130 Pages: 243-53
  • Peer Reviewed
• [Journal Article] Development of monoclonal antibodies for analyziand hematopoietic systems of common marmoset (2009)
  • Author(s): Kametan i Y, Suzuki D, Kohu K, Satake M, Suemizu H, Sasaki E, Ito T, Tamaoki N, Mizushima T, Ozawa M, Tani K, Kito M, Arai H, Koyanagi A, Yagita H, Habu S
  • Journal Title: Exp Hematol Volume: 37 Pages: 1318-1329
  • Peer Reviewed
• [Journal Article] Generation of transgenic non-human primates with germline transmission (2009)
  • Author(s): Sasaki E, Suemizu H, Shimada A, Hanazawa K, Oiwa R, Kamioka M, Tomioka I, Sotomaru Y, Hirakawa R, Eto T, Shiozawa S, Maeda T, Ito M, Ito R, Kito C, Yagihashi C, Kawai K, Miyoshi H, Tanioka Y, Tamaoki N, Habu S, Okano H, Nomura T
  • Journal Title: Nature Volume: 459 Pages: 523-527
  • Peer Reviewed
• [Journal Article] Generation of transgenic non-human primates with germline transmission (2009)
  • Author(s): Habu S
  • Journal Title: Nature 459 Pages: 523-527
  • Peer Reviewed
• [Journal Article] Development of monoclonal antibodies for analyzing immune and hematopoietic systems of common marmoset (2009)
  • Author(s): Habu S, Stake M
  • Journal Title: Exp.Hematol 37 Pages: 1318-1318
  • Peer Reviewed
• [Journal Article] Involvement of PU. 1 in mast cell/basophil-specific function of the human IL1RL1/ST2 promoter
  • Author(s): Baba Y, Maeda K, Yashiro T, Inage E, Niyonsaba F, Hara M, Suzuki R, Ohtsuka Y, Shimizu T, Ogawa H, Okumura K, and Nishiyama C
  • Journal Title: Allergol Int Volume: (in press)
  • NAID: 130004477155
  • Peer Reviewed
• [Journal Article] IL-10 controls Th2-type cytokine production and eosinophil infiltration in a mouse model of allergic airway inflammation.
  • Author(s): Kosaka S
  • Journal Title: Immunobiology Volume: (In Press)
  • Peer Reviewed
• [Presentation] IL-33受容体のマスト細胞・好塩基球特異的発現制御機構の解明 (2011)
  • Author(s): 馬場洋介、西山千春、前田啓子、鈴木竜洋、奥村康、大塚宜一、清水俊明
  • Organizer: 第61回日本アレルギー学会秋季学術大会
  • Year and Date: 2011-11-12
• [Presentation] Increase of transplanted human hematopoietic stem cells in transgenic NOG mice expressing human Jagged-1 in osteoblasts (2011)
  • Author(s): Negishi N, Ito R, Hozumi K, Ando K, Habu S
  • Organizer: 3rd international workshop on humanized mice
  • Place of Presentation: Pittsburgh, USA
• [Presentation] B細胞エピトープに基づく新規HER2ペプチドワクチンの抗腫瘍効果 (2010)
  • Author(s): 三朝博仁、亀谷美恵、片野いくみ、伊藤亮治、古川敦子、津田万里、今井浩三、垣生園子、幕内博康、徳田裕
  • Organizer: 第13回日本がん免疫学会総会
  • Year and Date: 2010-07-22
• [Presentation] The physiological significance of D114 for T cell development in the thymus(胸腺内T細胞分化におけるD114の生理的役割) (2009)
  • Author(s): Hozumi K, Hirano K, Nakano Y, Yagita H, Habu S
  • Organizer: 第39回日本免疫学会総愛・学術集会
  • Year and Date: 2009-12-12
• [Presentation] マスト細胞におけるc-kit分子の発言調節機構について (2009)
  • Author(s): 前田啓子、西山千春、戸倉智子、奥村康
  • Organizer: 第59回日本アレルギー学会秋季学術集会
  • Year and Date: 2009-10-31
• [Presentation] Evidence for the coupling of DNA replication control and lineage choice into CD4/8 thymocytes(CD4/8胸腺細胞分化とDNA複製制御は共役する) (2009)
  • Author(s): Sato T, Chiba T, Sugou T, Satake M, Habu S
  • Organizer: 第39回日本免疫学会総会・学術集会