Immunoregulation and therapeutic application of IL-17-producing gamm delta T cells

• Project/Area Number: 22790468
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Immunology
• Research Institution: Kyushu University
• Principal Investigator: SHIBATA Kensuke 九州大学, 生体防御医学研究所, 助教 (50529972)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2012: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2011: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2010: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 粘膜免疫 / IL-17産生gd T細胞 / サイトカイン / T細胞

Research Abstract

IL-17-producing gd T cells are involved in not only host defense against pathogens but also pathogenesis of various autoimmune diseases. We found that Notch-Hes1 pathway is critically involved in the development of IL-17-producing gd T cells. Furthermore, in infection mouse model with an opportunistic fungi, Candida albicans, IL-17-producing gd T cells had a protective role in the early stage of host defense by inducing neutrophil infiltration. Thus, our study provides a novel insight of development and function of IL-17-producing gd T cells.

Research Products

• [Journal Article] Naturally occurring PD-1+ memory phenotype CD8 T cells belong to nonconventional CD8 T cells and are cyclophosphamide-sensitive regulatory T cells (2013)
  • Author(s): Sakuraba K, Shibata K, Iwamoto Y, Yoshikai Y, Yamada H
  • Journal Title: J Immunol Volume: 190 Pages: 1560-6
  • Peer Reviewed
• [Journal Article] Naturally occurring PD-1+ memory phenotype CD8 T cells belong to nonconventional CD8 T cells and are cyclophosphamide-sensitive regulatory T cells. (2013)
  • Author(s): Sakuraba K
  • Journal Title: Journal of immunology Volume: 190 Issue: 4 Pages: 1560-1566
  • DOI: 10.4049/jimmunol.1202464
  • Peer Reviewed
• [Journal Article] Close link between development and function of gammadelta T cells (2012)
  • Author(s): Shibata K., et al
  • Journal Title: Microbiology and immunology Volume: (印刷中) Issue: 4 Pages: 217-227
  • DOI: 10.1111/j.1348-0421.2012.00435.x
  • Peer Reviewed
• [Journal Article] Innate memory phenotype CD4+ T cells play a role in early protection against infection by Listeria monocytogenes in a CD30L-dependent manner (2011)
  • Author(s): Umeda K, Sun X, Guo Y, Yamada H, Shibata K, Yoshikai Y.
  • Journal Title: Microbiol Immunol Volume: 55 Pages: 645-56
  • Peer Reviewed
• [Journal Article] IL-17 production by gammadelta T cells is important for the antitumor effect of Mycobacterium bovis bacillus Calmette-Guerin treatment against bladder cancer (2011)
  • Author(s): Takeuchi A, Dejima T, Yamada H, Shibata K, Nakamura R, Eto M, Nakatani T, Naito S, Yoshikai Y.
  • Journal Title: Eur J Immunol Volume: 41 Pages: 246-51
  • Peer Reviewed
• [Journal Article] Notch-Hes1 pathway is required for the development of IL-17-producing gammadelta T cells (2011)
  • Author(s): Shibata K, Yamada H, Sato T, Dejima T, Nakamura M, Ikawa T, Hara H, Yamasaki S, Kageyama R, Iwakura Y, Kawamoto H, Toh H, Yoshikai Y.
  • Journal Title: Blood Volume: 118 Pages: 586-93
  • Peer Reviewed
• [Journal Article] The central role of CD30L/CD30 interactions in allergic rhinitis pathogenesis in mice (2011)
  • Author(s): Fuchiwaki T, Sun X, Fujimura K, Yamada H, Shibata K, Muta H, Podack ER, Kawauchi H, Yoshikai Y.
  • Journal Title: Eur J Immunol Volume: 41 Pages: 2947-54
  • Peer Reviewed
• [Journal Article] Protective role of naturally occurring interleukin-17A-producing gammadelta T cells in the lung at the early stage of systemic candidiasis in mice (2011)
  • Author(s): Dejima T, Shibata K, Yamada H, Hara H, Iwakura Y, Naito S, Yoshikai Y
  • Journal Title: Infect Immun Volume: 79 Pages: 4503-10
  • Peer Reviewed
• [Journal Article] Notch-Hes1 pathway is required for the development of IL-17-producing Yδ T cells (2011)
  • Author(s): K.Shibata
  • Journal Title: Blood Volume: 118 Issue: 3 Pages: 586-593
  • DOI: 10.1182/blood-2011-02-334995
  • Peer Reviewed
• [Journal Article] Protective role of naturally occurring interleukin-17A-producing Yδ T cells in the lung at the early stage of systemic candidiasis in mice (2011)
  • Author(s): T.Dejima
  • Journal Title: Infect Immun Volume: 79 Issue: 11 Pages: 4503-4510
  • DOI: 10.1128/iai.05799-11
  • Peer Reviewed
• [Journal Article] CD30 ligand is a target for a novel biological therapy against allergic rhinitis (2011)
  • Author(s): Fuchiwaki T, et al
  • Journal Title: Eur.J.Immunol Volume: 41 Issue: 10 Pages: 2947-2954
  • DOI: 10.1002/eji.201141423
  • Peer Reviewed
• [Journal Article] IL-17 production by gammadelta T cells is important for the antitumor effect of Mycobacterium bovis bacillus Calmette-Guerin treatment against bladder cancer (2011)
  • Author(s): Takeuchi, et al
  • Journal Title: European Journal of Immunology Volume: 41 Pages: 246-251
  • Peer Reviewed
• [Journal Article] CD30 ligand/CD30 plays a critical role in Th17 differentiation in mice (2010)
  • Author(s): Sun X, Yamada H, Shibata K, Muta H, Tani K, Podack ER, Yoshikai Y.
  • Journal Title: J Immunol Volume: 185 Pages: 2222-30
  • Peer Reviewed
• [Journal Article] CD30 ligand is a target for a novel biological therapy against colitis associated with Th17 responses (2010)
  • Author(s): Sun X, Yamada H, Shibata K, Muta H, Tani K, Podack ER, Iwakura Y, Yoshikai Y
  • Journal Title: J Immunol Volume: 185 Pages: 7671-80
  • Peer Reviewed
• [Presentation] Notch-RBP-Jκ-IL-7 receptor alpha axis is essential for the maintenance of IL-17-producing γδ T cells (2012)
  • Author(s): 柴田健輔
  • Organizer: 日本免疫学会
  • Place of Presentation: 神戸, 日本
  • Year and Date: 2012-12-07
• [Presentation] Intrathymic programming of murine gd T cells by Notch signaling (2012)
  • Author(s): 柴田健輔
  • Organizer: gd T cell conference
  • Place of Presentation: Freiburg, Germany
  • Year and Date: 2012-06-01
• [Presentation] Notch-RBP-Jκ-IL-7 receptor alpha axis is essential for the maintenance of IL-17-producing γδ T cells (2012)
  • Author(s): 柴田健輔
  • Organizer: 日本免疫学会
  • Place of Presentation: 神戸
• [Presentation] Notch-IL-7Rα経路は自然発生IL-17産生γδ T細胞の維持に必須である (2012)
  • Author(s): 中村真隆
  • Organizer: 日本生体防御学会
  • Place of Presentation: 東京
• [Presentation] Notch、γδTCRシグナルによるγδ T細胞機能分化制御 (2012)
  • Author(s): 柴田健輔
  • Organizer: 日本生体防御学会
  • Place of Presentation: 東京
• [Presentation] NotchシグナルはIL-17産生γδ T細胞の維持に必須である (2012)
  • Author(s): 柴田健輔
  • Organizer: 京都 T cell conference
  • Place of Presentation: 京都
• [Presentation] Intrathymic programming of murine gd T cells by Notch signaling (2012)
  • Author(s): 柴田健輔
  • Organizer: gd T cell conference
  • Place of Presentation: フライブルグ、ドイツ
• [Presentation] IL-7-receptor-α-mediated signaling is required for the development of naturally occurring IL-17-producing γδ T cells in the adult thymus (2011)
  • Author(s): 中村真隆、柴田健輔
  • Organizer: 日本免疫学会
  • Place of Presentation: 千葉, 日本
  • Year and Date: 2011-11-27
• [Presentation] Naturally occurring IL-17-producing γδ T cells commit at the DN2 stage of mouse fetal thymus in Notch-dependent manner (2011)
  • Author(s): 柴田健輔
  • Organizer: 日本免疫学会
  • Place of Presentation: 千葉
  • Year and Date: 2011-11-27
• [Presentation] A protective role of naturally occurring IL-17A-producing γδ T cells in the lung at the early stage of systemic candidiasis in mice (2011)
  • Author(s): 出嶋卓
  • Organizer: 日本免疫学会
  • Place of Presentation: 千葉
  • Year and Date: 2011-11-27
• [Presentation] Notch-Hes1経路は自然発生IL-17産生γδT細胞分化に必要である (2011)
  • Author(s): 柴田健輔
  • Organizer: 日本生体防御学会
  • Place of Presentation: 沖縄
  • Year and Date: 2011-06-29
• [Presentation] 胸腺におけるγδT細胞機能獲得機構の解析 (2011)
  • Author(s): 柴田健輔
  • Organizer: 京都T cell conference
  • Place of Presentation: 京都
  • Year and Date: 2011-06-11
• [Presentation] The Basic Helix-Loop-Helix protein HES1 controls the differentiation of naturally occurring interleukin (IL)-17-producing γδ T cells (2010)
  • Author(s): 柴田健輔
  • Organizer: 14th International Congress Of Immunology
  • Place of Presentation: 神戸、日本
  • Year and Date: 2010-08-27
• [Presentation] The Basic Helix-Loop-Helix protein HES1 controls the differentiation of naturally occurring interleukin (IL)-17-producing γδ T cells. (2010)
  • Author(s): Kensuke Shibata
  • Organizer: International Congress of Immunology
  • Place of Presentation: 神戸市
  • Year and Date: 2010-08-27
• [Presentation] A protective role of IL-17-producing yδ T cells in lung against systemic candidiasis (2010)
  • Author(s): Takashi Dejima
  • Organizer: International Congress of Immunology
  • Place of Presentation: 神戸市
  • Year and Date: 2010-08-27
• [Presentation] The basic Helix-loop-Helix protein HES1は自然発生IL-17産生γδ T細胞分化に必要である (2010)
  • Author(s): 柴田健輔
  • Organizer: 生体防御学会
  • Place of Presentation: 仙台市
  • Year and Date: 2010-07-24
• [Presentation] The Basic Helix-Loop-Helix protein HES1, is required for the differentiation of naturally occurring interleukin (IL)-17-producing γδ T cells (2010)
  • Author(s): Yasunobu Yoshikai
  • Organizer: Kyoto T cell conference
  • Place of Presentation: 京都市
  • Year and Date: 2010-06-04
• [Presentation] The Basic Helix-Loop-Helix protein HES1, is required for the differentiation of naturally occurring interleukin(IL)-17-producing gd T cells (2010)
  • Author(s): 柴田健輔
  • Organizer: gd T cell conferenc
  • Place of Presentation: Kiel, Germany
  • Year and Date: 2010-05-19
• [Presentation] The Basic Helix-Loop-Helix protein HES1, is required for the differentiation of naturally occurring interleukin (IL)-17-producing γδ T cells. (2010)
  • Author(s): Kensuke Shibata
  • Organizer: γδ T cell conference
  • Place of Presentation: Kiel, Germany
  • Year and Date: 2010-05-19
• [Book] IL-17産生gd T細胞の分化と活性化 (2012)
  • Author(s): 柴田健輔
  • Total Pages: 5
  • Publisher: 臨床免疫・アレルギー科
• [Book] 臨床免疫・アレルギー科 (2012)
  • Author(s): 柴田健輔
  • Total Pages: 5
  • Publisher: 科学評論社
• [Remarks]
  • URL: http://www.bioreg.kyushu-u.ac.jp/kansenseigyo/home0.html