Immune regulation by the IL-6/IL-12 family cytokines

2010 Fiscal Year Final Research Report

• Project/Area Number: 20370049
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Tokyo Medical University
• Principal Investigator: YOSHIMOTO Takayuki Tokyo Medical University, 医学部, 教授 (80202406)
• Project Period (FY): 2008 – 2010
• Keywords: IL-22 / IL-23 / IL-27 / IL-35

Research Abstract

The IL-6/IL-12 family cytokines play an important role in the regulation of immune responses as pro-inflammatory cytokines, inducers of helper T differentiation, and effector molecules. In the present study, we elucidated the molecular mechanisms whereby these cytokines are produced and exert their biological responses, the role in various disease models, and the possibility of clinical application of these cytokines and the identification of a novel composite molecule. Therefore, the present results will open up a novel avenue to the therapy of various diseases including cancer and autoimmune diseases as well as the identification of a new cytokine.

Research Products

• [Journal Article] Notch signaling drives IL-22 secretion in CD4^+ T cells by stimulating the aryl hydrocarbon receptor. (2010)
  • Author(s): Alam M.S., Maekawa Y., Kitamura A., Tanigaki K., Yoshimoto T., Kishiara K., Yasutomo K.
  • Journal Title: Proc.Natl.Acad.Sci.U.S.A. 107 Pages: 5943-5948
• [Journal Article] Anti-melanoma immunotherapy : Clinical and preclinical applications of IL-12 family members. (2010)
  • Author(s): Nagai H., Oniki S., Fujiwara S., Yoshimoto T., Nishigori C.
  • Journal Title: Immunotherapy 5 Pages: 697-709
• [Journal Article] Antitumor activities of interleukin-27 on melanoma. (2010)
  • Author(s): Nagai H., Oniki S., Fujiwara S., Xu M. Mizoguchi I., Yoshimoto T., Nishigori, C.
  • Journal Title: Endocr.Metab.Immune Disord.Drug Targets 10 Pages: 41-46
• [Journal Article] Natural occurring IL-17 producing T cells regulate the initial phase of neutrophil mediated airway responses. (2009)
  • Author(s): Tanaka S., Yoshimoto T., Naka T., Nishida K., Murakami M., Hirano T., Nakae S., Iwakura Y, Cua D., Kubo M.
  • Journal Title: J.Immunol. 183 Pages: 7523-7530
• [Journal Article] Interleukins and cancer immunotherapy. (2009)
  • Author(s): Yoshimoto T., Morishima N., Okumura M., Chiba Y., Xu M., Mizuguchi J.
  • Journal Title: Immunotherapy 1 Pages: 825-844
• [Journal Article] TGF-b is necessary for induction of IL-23R and Th17 differentiation by IL-6 and IL-23. (2009)
  • Author(s): Morishima N., Mizoguchi I., Takeda K., Mizuguchi J., Yoshimoto T.
  • Journal Title: Biochem.Biophys.Res.Commun. 286 Pages: 105-110
• [Journal Article] Expression of Interlukins-23 and 27 leads to successful gene therapy of hepatocellular carcinoma. (2009)
  • Author(s): Hu P., Hu H.D., Chen M., Peng M.L., Tang L., Tang K.F., Matsui M., Belladonna M.L., Yoshimoto T., Zhang D.Z., Xiang R., Ren H.
  • Journal Title: Mol.Immunol. 46 Pages: 1654-1662
• [Journal Article] IL-27 activates natural killer (NK) cells and suppresses NK-resistant head and neck squamous cell carcinoma through inducing antibody-dependent cellular cytotoxicity. (2009)
  • Author(s): Matsui M., Kishida T., Nakano H., Yoshimoto K., Shin-Ya M., Shimada T., Nakai S., Imanishi J., Yoshimoto T., Hisa Y., Mazda O.
  • Journal Title: Cancer Res. 69 Pages: 2523-2530
• [Journal Article] Interleukin-27 : biological properties and application to immunotherapy of cancer. (2008)
  • Author(s): Yoshimoto T., Morishima N., Okumura M., Chiba Y, Onishi K., Mizoguchi I., Mizuguchi J.
  • Journal Title: Trend.Cancer Res. 4 Pages: 93-103
• [Journal Article] Anti-proliferative activity of IL-27 on melanoma. (2008)
  • Author(s): Yoshimoto T., Morishima N., Mizoguchi I., Oniki S., Nagai H., Oka M., Nishigori C., Mizuguchi J.
  • Journal Title: J.Immunol. 180 Pages: 6527-6535
• [Journal Article] IFN-g is a therapeutic target molecule for prevention of postoperative adhesion formation. (2008)
  • Author(s): Kosaka H., Yoshimoto T., Yoshimoto T., Fujimoto J., Nakanishi K.
  • Journal Title: Nat.Med. 14 Pages: 437-441
• [Journal Article] STAT3 is indispensable to IL-27-mediated cell proliferation but not to IL-27-induced Th1 differentiation and suppression of proinflammatory cytokine production. (2008)
  • Author(s): Owaki T., Asakawa M., Morishima N., Mizoguchi J. Takeda K., Fukai F., Mizuguchi J., Yoshimoto T.
  • Journal Title: J.Immunol. 180 Pages: 2903-2911
• [Journal Article] Interleukin-27 directly induces differentiation in hematopoietic stem cells. (2008)
  • Author(s): Seita J., Asakawa M., Ooehara J., Takayanagi S., Morita Y, Watanabe N., Fujita K., Kudo M., Mizuguchi J., Ema H., Nakauchi H., Yoshimoto T.
  • Journal Title: Blood 111 Pages: 1903-1912
• [Journal Article] IL-23 gene therapy for mouse bladder tumor cell lines.
  • Author(s): Kuramoto T., Fujii R., Nagai H., Belladonna M.L., Yoshimoto T., Kohjimoto Y., Inagaki T., Hara I.
  • Journal Title: BJU Int. (in press)
• [Journal Article] Local expression of IL-27 ameliorates collagen induced arthritis.
  • Author(s): Pickens S.R., Volin M.V., Mandelin II A.M., Matsui M., Yoshimoto T., Shahrara S.
  • Journal Title: Arthritis Rheum. (in press)
• [Journal Article] IL-27 suppresses RANKL expression in CD4^+ T cells in part through STAT3.
  • Author(s): Kamiya S., Okumura M., Chiba Y., Nakamura C., Fukawa T., Nimura N., Mizuguchi J., Wada S., Yoshimoto, T.
  • Journal Title: Immuuol.Let. (in press)
• [Journal Article] Regulation of antitumor immune responses by the IL-12 family cytokines, IL-12, IL-23 and IL-27.
  • Author(s): Xu M., Mizoguchi I., Morishima N., Chiba Y., Mizuguchi J., Yoshimoto T.
  • Journal Title: Clin.Dev.Immunol. (in press)
• [Journal Article] A pivotal role for interleukin-27 in CD8^+ T cell functions and generation of cytotoxic T lymphocytes.
  • Author(s): Morishima N., Mizoguchi I., Okumura M., Chiba Y., Xu M., Shimizu M., Matsui M., Mizuguchi J., Yoshimoto T.
  • Journal Title: J.Biomed.Biotech. (in press)
• [Presentation] サイトカインによる免疫制御 (2011)
  • Author(s): 善本隆之
  • Organizer: 第34回東京医科大学・医科学フォーラム
  • Place of Presentation: 東京
  • Year and Date: 2011-02-22
• [Presentation] IL-6/IL-12関連ヘテロダイマーサイトカインによる免疫制御と治療応用 (2011)
  • Author(s): 善本隆之
  • Organizer: 第1回東京医科大学・東京薬科大学生命科学部合同シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2011-01-29
• [Presentation] IL-27の抗腫瘍作用におけるマクロファージの役割 (2010)
  • Author(s): 清水本武、佐藤真友美、小倉潔、武田康隆、水口純一郎、善本隆之
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 20100922-20100924
• [Presentation] Antitumor activity of IL-27 by augmentation of histocompatibility antigens. (2010)
  • Author(s): Shimizu M., Mizuguchi J., Yoshimoto T.
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: Kobe, Japan
  • Year and Date: 20100822-20100827
• [Presentation] IL-27 induces rapid up-regulation of Notch l expression critical for IL-10 production in CD4^+ T cells. (2010)
  • Author(s): Morishima N., Xu M., Mizoguchi I., Chiba Y., Yasutomo K., Mizuguchi J., Yoshimoto T.
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: Kobe, Japan
  • Year and Date: 20100822-20100827
• [Presentation] A protective role for IL-23 in acute hepatitis model by inducing IL-22 production. (2010)
  • Author(s): Xu M., Morishima N., Mizoguchi I., Chiba Y., Fujita K., Kuroda M., Cua D.J., Yasutomo K., Mizuguchi J., Yoshimoto T.
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: Kobe, Japan
  • Year and Date: 20100822-20100827
• [Presentation] Regulation of Th cell differentiation by IL-23p19 produced by activated CD4^+ T cells. (2009)
  • Author(s): Chiba Y, Mizoguchi I., Mizuguchi J., Yoshimoto T.
  • Organizer: 第39回日本免疫学会総会
  • Place of Presentation: 大阪
  • Year and Date: 20091202-20091204
• [Presentation] IL-27による組織適合抗原と抗腫瘍作用の増強 (2009)
  • Author(s): 清水本武、水口純一郎、善本隆之
  • Organizer: 第39回日本免疫学会総会
  • Place of Presentation: 大阪
  • Year and Date: 20091202-20091204
• [Presentation] IL-27はNK細胞を活性化しADCCを介してNK抵抗性頭頸部扁平上皮癌を抑制する (2009)
  • Author(s): 松井雅裕、岸田綱郎、中野宏、吉本公一郎、新屋政春、島田剛敏、中井茂,今西二郎、善本隆之、久育男、松田修
  • Organizer: 第39回日本免疫学会総会
  • Place of Presentation: 大阪
  • Year and Date: 20091202-20091204
• [Presentation] IL-27による組織適合抗原の発現上昇と抗腫瘍機構の解析 (2009)
  • Author(s): 清水本武、佐藤真友美、小倉潔、武田康隆、水口純一郎、善本隆之
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 20091001-20091003
• [Presentation] IL-27 suppresses RANKL expression in CD4^+ T cells partly through STAT3. (2009)
  • Author(s): Kamiya S., Okumura M., Chiba Y, Fukawa T., Nakamura C., Nimura N., Mizuguchi J., Yoshimoto T., Wada S.
  • Organizer: ASBMR 31^<st> Annual Meeting.
  • Place of Presentation: Denver, Colorado
  • Year and Date: 20090911-20090915
• [Presentation] IL-27はNK細胞を活性化しADCCを介してNK抵抗性頭頸部扁平上皮癌を抑制する (2009)
  • Author(s): 松井雅裕、岸田綱郎、中野宏、吉本公一郎、新屋政春、島田剛敏、中井茂、今西二郎、善本隆之、久育男、松田修
  • Organizer: 第72回日本インターフェロン・サイトカイン学会
  • Place of Presentation: 京都
  • Year and Date: 20090626-20090627
• [Presentation] Plasmacytoid dendritic cells are crucial for Th17 differentiation. (2009)
  • Author(s): Ishifune C., Maekawa Y., Yoshimoto T., Yasutomo K.
  • Organizer: The 96^<th> Annual Meeting of The American Association of Immunologists.
  • Place of Presentation: Seattle, Washington
  • Year and Date: 20090508-20090512
• [Presentation] Potent immune regulatory activity of IL-10^|IFN-y^| Tr1 cells induced and expanded by IL-27 and TGF-β. (2009)
  • Author(s): Yoshimoto T., Morishima N., Onishi K., Torii M., Kato T., Mizuguchi J.
  • Organizer: Keystone Symposia on Regulatory T Cells.
  • Place of Presentation: Keystone, Colorado
  • Year and Date: 20090301-20090306
• [Presentation] IL-27とTGF-β1刺激による効果的なIL-10産生Tr1細胞の誘導と増幅 (2008)
  • Author(s): 森嶋紀子、鳥井美江、加藤琢磨、水口純一郎、善本隆之
  • Organizer: 第38回日本免疫学会総会
  • Place of Presentation: 京都
  • Year and Date: 20081201-20081203
• [Presentation] IL-33で刺激されたマスト細胞は制御性T細胞の増幅を介して炎症抑性能を発揮する (2008)
  • Author(s): 大保木啓介、大野建州、梶原直樹、須藤カツ子、善本隆之、須藤一、奥村康、小川秀興、齋藤博久、中江進
  • Organizer: 第38回日本免疫学会総会
  • Place of Presentation: 京都
  • Year and Date: 20081201-20081203
• [Presentation] IL-27によるメラノーマに対するin vivo抗腫瘍機構の解析 (2008)
  • Author(s): 清水本武、水口純一郎、善本隆之
  • Organizer: 第38回日本免疫学会総会
  • Place of Presentation: 京都
  • Year and Date: 20081201-20081203
• [Presentation] Plasmacytoid dendritic cells are crucial for Th17 differentiation. (2008)
  • Author(s): Ishifune C., Maekawa Y., Yoshimoto T., Yasutomo, K.
  • Organizer: 第38回日本免疫学会総会
  • Place of Presentation: 京都
  • Year and Date: 20081201-20081203
• [Presentation] Inhibition of RANKL expression in CD4^+ T cells by IL-27 partially through STAT3 dependent mechanism. (2008)
  • Author(s): Chiba Y., Kamiya S., Mizuguchi J., Yoshimoto T.
  • Organizer: 第38回日本免疫学会総会
  • Place of Presentation: 京都
  • Year and Date: 20081201-20081203
• [Presentation] IL-27による抗腫瘍機構の解析 (2008)
  • Author(s): 清水本武、佐藤真友美、小倉潔、西籐泰昌、武田康隆、水口純一郎、善本隆之
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 20081028-20081030
• [Presentation] IL-12.IL-17 axisによるウイルス感染防御における増強機構の解析 (2008)
  • Author(s): 高山俊輔、大野悟史、磯田明宏、守屋修、林秀徳、岩倉洋一郎、善本隆之、赤塚俊隆、松井政則
  • Organizer: 日本薬学会第128年会
  • Place of Presentation: 仙台
  • Year and Date: 20080328-20080330
• [Remarks] ホームページ
  • URL: http://www.tokyo-med.ac.jp/d-idrc/nannkenn_top.html