Screening of the target genes of IL-6 Amp that promotes autoimmune diseases

• Project/Area Number: 22790464
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Immunology
• Research Institution: Osaka University
• Principal Investigator: OGURA Hideki 大阪大学, 大学院・医学系研究科, 助教 (20573174)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: IL-6アンプ / IL-6 Amp / 4ステップモデル / 自己免疫 / 慢性炎症 / 線維芽細胞 / IL-17 / Ccl20 / 自己免疫疾患 / 関節炎 / IL-17A / CCL20 / IL-6 / IL-6Amp

Research Abstract

IL-6 Amp is important for autoimmune diseases and chronic inflammation. In order to identify the target molecules of IL-6 Amp, several genome-wide screening methods were carried out. As results, an inflammatory chemokine Ccl20 that enhances the recruitment of a subset of T cells is identified as a key target. With those findings," a four-step model" for organ-specific autoimmune diseases was presented. Finally, a soluble molecule highly presented in the patients with an autoimmune disease was found to be important for regulating IL-6 Amp, that opens new possibilities for the drug development.

Research Products

• [Journal Article] Local microbleeding facilitates IL-6-and IL-17-dependent arthritis in the absence of tissue antigen recognition by activated T cells (2011)
  • Author(s): Murakami M*, Okuyama Y*, Ogura H*, Asano S, Arima Y, Tsuruoka M, Harada M, Kanamoto M, Sawa Y, Iwakura Y, Takatsu K, Kamimura D, Hirano T(* equally contributed to this paper.)
  • Journal Title: Journal of Experimental Medicine Volume: 208(1) Pages: 103-114
  • Peer Reviewed
• [Journal Article] Local microbleeding facilitates IL-6- and IL-17-dependent arthritis in the absence of tissue antigen recognition by activated T cells. (2011)
  • Author(s): Murakami M, Ogura H, et al.(equally contributed to this paper)
  • Journal Title: Journal of Experimental Medicine Volume: 208(1) Pages: 103-114
  • Peer Reviewed
• [Journal Article] IL-6誘導性の"炎症アンプ"と自己免疫疾患 (2010)
  • Author(s): 小椋英樹、村上正晃、平野俊夫
  • Journal Title: 医学のあゆみサイトカインと疾患 Volume: 234 Pages: 495-500
• [Journal Article] IL-6誘導性の"炎症アセプ"と自己免疫疾患 (2010)
  • Author(s): 小椋英樹、村上正晃、平野俊夫
  • Journal Title: 医学のあゆみサイトカインと疾患 Volume: 234 Pages: 495-500
• [Presentation] A zinc finger motif containing potein, ZFZ regulates IL-6 amplifier activation via regulating NF-kB activity and promotes an autoimmune arthritis (2011)
  • Author(s): 小椋英樹、村上正晃、他
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ
  • Year and Date: 2011-11-29
• [Presentation] Zinc finger motif containing protein A, ZFA regulates IL-6 amplifier activation via regulating NF-kB activity and promotes anautoimmune arthritis (2011)
  • Author(s): 勝沼功吉、小椋英樹、村上正晃、他
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ
  • Year and Date: 2011-11-29
• [Presentation] A protein kinase, PKX is involved in the development of autoimmune diseases via regulating the IL-6 amplifier activation (2011)
  • Author(s): 諸井亜理紗、小椋英樹、村上正晃、他
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ
  • Year and Date: 2011-11-29
• [Presentation] A protein kinase, PKX is involved in the development of a utoimmune diseases via regulating the IL-6 amplifier activation (2011)
  • Author(s): 諸井亜理紗、小椋英樹、村上正晃, 他
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ
  • Year and Date: 2011-11-29
• [Presentation] A Four-step Model for MHC Class II-Associated Autoimmune Diseases (2011)
  • Author(s): OKUYAMA Y, OGURA H, MURAKAMI M, 他
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ
  • Year and Date: 2011-11-28
• [Presentation] An ENU-mutant mouse, which increased a stress signaling in naive T cells (2011)
  • Author(s): KAMIMURA D, OGURA H, MURAKAMI M, 他
  • Organizer: 第40回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ
  • Year and Date: 2011-11-28
• [Presentation] A zinc finger motif containing protein regulttes the activation of the IL-6 amplifier, which is a critical for the development of an autoimmune arthritis (2010)
  • Author(s): H. Ogura, H. Masaya, E. Sanda, Y. Okuyama, D Kamimura, M. Murakami, T. Hirano
  • Organizer: 60^<th> Fujihara Seminar" Zinc Signaling and Cellular Funcrions"
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2010-10-30
• [Presentation] A zinc finger motif containing protein regulttes the activation of the IL-6 amplifier, which is a critical for the development of an autoimmune arthritis (poster) (2010)
  • Author(s): H.Ogura, M.Murakami, T.
  • Organizer: 60^<th> Fujihara Seminar "Zinc Signaling and Cellular Funcrions"
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2010-10-30
• [Presentation] IL-6-meidated positive regulation of Foxp3^+ CD8^+ T cells is critical for the development of autoimmune diseases (2010)
  • Author(s): Tsuruoka M, Nakagawa T, Kamimura D, Ogura H, Okuyama Y, Arima Y, Hirano T, Murakami M
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: 神戸国際展示場
  • Year and Date: 2010-08-26
• [Presentation] IL-6-meidated positive regulation of Foxp3^+CD8^+ T cells iscritical for the development of autoimmune diseases (poster) (2010)
  • Author(s): Tsuruoka M, Oeura H, et al.
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: 神戸国際展示場
  • Year and Date: 2010-08-26
• [Presentation] Specific antigen recognition by CD4+ T cells is not required for a MHC class II-associated autoimmune arthritis (2010)
  • Author(s): Okuyama Y, Ogura H, Asano S, Kanamoto M, Arima Y, Iwakura Y, Takatsu K, Kamimura D, Murakami M, Hirano T
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: 神戸国際展示場
  • Year and Date: 2010-08-24
• [Presentation] IL-6 plays roles not only for developing Th17 but also for inducing an IL-6 amplifier in autoimmune diseases (2010)
  • Author(s): H. Ogura, M. Murakami, Y. Okuyama, M. Tsuruoka, C. Kitabayashi, M. Kanamoto, M. Nishihara, Y. Iwakura, K. Takatsu, D. Kamimura, T. Hirano
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: 神戸国際展示場
  • Year and Date: 2010-08-24
• [Presentation] IL-6 plays roles not only for developing Th17 but also for inducing an IL-6 amplifier in autoimmune diseases (poster and oral presentation) (2010)
  • Author(s): H.Ogura, M.Murakami, T.Hirano, et al.
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: 神戸国際展示場
  • Year and Date: 2010-08-24
• [Presentation] Specific antigen recognition by CD4+T cells is not required for a MHC class II-associated autoimmune arthritis (poster) (2010)
  • Author(s): Okuyama Y, Ogura H, et al.
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: 神戸国際展示場
  • Year and Date: 2010-08-24
• [Presentation] IL-6-mediated STAT3 signaling in T cells directs the development of Th17 with a minimum effect on that of Treg in vivo (2010)
  • Author(s): M. Harada, M. Nishihara, H. Ogura, N. Ueda, M. Tsuruoka, C. Kitabayashi, F. Fuji, H. Aono, K. Ishihara, E. Huseby, U. A. K. Betz, M. Murakami, T. Hirano
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: 神戸国際展示場
  • Year and Date: 2010-08-23
• [Presentation] IL-6-mediated STAT3 signaling in T cells directs the development of Th17 with a minimum effect on that of Treg in vivo (poster) (2010)
  • Author(s): M.Harada, H.Ogura, et al.
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: 神戸国際展示場
  • Year and Date: 2010-08-23
• [Remarks]
  • URL: http://www.med.osaka-u.ac.jp/pub/molonc/www/jpn/achievements/4-step-model.html
• [Remarks]
  • URL: http://www.med.osaka-u.ac.jp/pub/molonc/www/jpn/achievements/4-step-model.html
• [Remarks]
  • URL: http://www.med.osaka-u.ac.jp/pub/molonc/www/jpn/achievements/4-step-model.html