Controlling of chronic inflammatory diseases via regulation of inflammation stroma cells

2011 Fiscal Year Final Research Report

• Project/Area Number: 21390120
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Osaka University
• Principal Investigator: MURAKAMI Masaaki 大阪大学, 大学院・生命機能研究科, 准教授 (00250514)
• Co-Investigator(Kenkyū-buntansha): KAMIMURA Daisuke 大阪大学, 大学院・生命機能研究科, 助教 (20391922)
• Project Period (FY): 2009 – 2011
• Keywords: 炎症 / 非免疫系細胞 / サイトカイン / IL-6

Research Abstract

We defined the inflammation stroma cells as cells having excessive chenokine production after NFkB and STAT3 stimulation. The inflammation stroma cells have type 1 collagen molecules and include endothelial cells, fibroblasts, astrocytes, and epithelial cells. The main founding in this project is that excessive activation of the he inflammation stroma cells by an excessive neural activation particularly via sympathetic neuron' s creates a gateway for immune cells in blood vessels including autoreactive CD4+ T cells followed by the development of an autoimmune disease.

Research Products

• [Journal Article] Intestinal CX3C chemokine receptor 1high(CX3CRlhigh) myeloid cells prevent T-cell-dependent colitis (2012)
  • Author(s): Kayama H., Ueda, Y., Sawa, Y., Jeon, S. G., Ma, J. S. Okumura, R., Kubo, A., Ishii, M., Okazaki, T., Murakami, M., Yamamoto, M., Yagita, H., and Takeda, K
  • Journal Title: Natl. Acad. Sci. USA Volume: 109 Pages: 5010-5015
  • Peer Reviewed
• [Journal Article] Regional neural activation directly influences immune signals in the CNS (2012)
  • Author(s): Arima, Y, M. Harada, D. Kamimura, J.-H. Park, F. Kawano, F. E. Yull, T. Kawamoto Y. Iwakura, U. A. K. Betz, G. Marquez, T. S. Blackwell, Y. Ohira, T. Hirano, and M. Murakami
  • Journal Title: Cell Volume: 148 Pages: 447-457
  • Peer Reviewed
• [Journal Article] SIRPalpha/ CD172a Regulates Eosinophil Homeostasis (2011)
  • Author(s): Garcia, N. V., Umemoto, E., Saito, Y., Yamasaki, M., Hata, E., Matozaki, T., Murakami, M., Jung, Y. J., Woo, S. Y., Seoh, JY., Jang, M. H., Aozasa, K., Miyasaka, M
  • Journal Title: J. Immunol Volume: 187(5) Pages: 2268-2277
  • Peer Reviewed
• [Journal Article] (equal contribution) 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., Y. Okuyama, H. Ogura, S. Asano, Y. Arima, M. Tsuruoka, M. Harada, M. Kanamoto, Y. Sawa, Y. Iwakura, K. Takatsu, D. Kamimura, T. Hirano.
  • Journal Title: J. Exp. Med Volume: 208 Pages: 103-114
  • Peer Reviewed
• [Journal Article] homeostasis and signaling in health and diseases : Zinc signaling (2011)
  • Author(s): Fukada, T., Nishida, K., Yamazaki, S., Murakami, M., and Hirano, T. Zinc
  • Journal Title: J Biol Inorg Chem Volume: 16 Pages: 1123-1134
  • Peer Reviewed
• [Journal Article] Zinc in Allergy, Autoimmune, and Hard and Connective Tissue Diseases (2011)
  • Author(s): Nishida, K., Fukada, T., Yamasaki, S., Murakami, M., and Hirano, T
  • Journal Title: Zinc in Human Health
• [Journal Article] Zinc suppresses Th17 development viainhibition of STAT3 activation (2010)
  • Author(s): Kitabayashi C., T. Fukada, M. Kanamotol, W. Ohashi, S. Hojyo, T Atsumi, N. Ueda, I. Azuma, H. Hirota, M. Murakami, and T. Hirano
  • Journal Title: Int. Immunol Volume: 22(5) Pages: 375-386
  • Peer Reviewed
• [Journal Article] IL-6 positively regulates Foxp3+ CD8+ T cells in vivo (2010)
  • Author(s): Nakagawa T., Tsuruoka, M., Ogura, H., Okuyama, Y., Arima, Y., Hirano, T., and Murakami, M
  • Journal Title: Int. Immunol Volume: 22(2) Pages: 129-139
  • Peer Reviewed
• [Journal Article] IFN-γexpression in CD8+ T cells regulated by IL-6 signal is involved in superantigen-mediated CD4+ T cell death (2009)
  • Author(s): Atsumi, T., Sato, M., Kamimura, D., Moroi, A., Iwakura, Y., Betz, U. A. K., Yoshimura, A., Nishihara, M., Hirano, T., and Murakami, M
  • Journal Title: Int. Immunol Volume: 21(1) Pages: 73-80
  • Peer Reviewed
• [Journal Article] Hepatic IL-7 expression regulates T cell Responses (2009)
  • Author(s): Sawa, Y., Y. Arima, H. Ogura, C. Kitabayashi, J. J. Jiang, T. Fukushima, D. Kamimura, T. Hirano, and M. Murakami
  • Journal Title: Immunity Volume: 30 Pages: 447-457
  • Peer Reviewed
• [Journal Article] A four step model for the IL-6 amplifier, a regulator of chromic inflammations in tissue specific MHC class II-associated autoimmune diseases
  • Author(s): Murakami, M. and T. Hirano
  • Journal Title: Front. Immun Volume: 2 Pages: 22
  • DOI: doi:10.3389/fimmu.2011.00022
  • Peer Reviewed
• [Presentation] The IL-6 amplifier activation, a key player of inflammation, in human diseases and disorders (2011)
  • Author(s): Masaaki Murakami
  • Organizer: 第40回日本免疫学会学術集会シンポジューム招待講演於
  • Place of Presentation: 幕張メッセ(千葉県)
  • Year and Date: 2011-11-27
• [Presentation] Zinc signaling and Inflammation (2011)
  • Author(s): Masaaki Murakami
  • Organizer: The 5th International Conference on Metals and Genetics(ICMG2011)シンポジユーム招待講演
  • Place of Presentation: Kobe International Conference Center, Kobe, Japan
  • Year and Date: 2011-09-05
• [Presentation] IL-6 amplifier and human diseases (2011)
  • Author(s): Masaaki Murakami
  • Organizer: RCAI-CGM Joint Meeting,招待講演,理化学研究所免疫アレルギー科学総合研究センター
  • Place of Presentation: 神奈川県
  • Year and Date: 2011-06-17
• [Presentation] Zinc and CD4+ T cell-mediated autoimmune diseases (2010)
  • Author(s): Masaaki Murakami, Chika Kitabayashi, Toshiyuki Fukada, Minoru Kanamoto, Wakana Ohashi, Shintaro Ho jyo, Toru Atsumi, Naoko Ueda, Ichiro Azuma, Hiroshi Hirota, and Toshio Hirano
  • Organizer: The 60th Fujihara Seminar Zinc Signaling and Cellular Functions
  • Place of Presentation: Osaka International Convention Center
  • Year and Date: 20101029-31
• [Presentation] Liver as a regulator of T cells (2009)
  • Author(s): Murakami M., and T. Hirano
  • Organizer: The 5th International Workshop of Kyoto T Cell Conference 2009
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 20090601-04
• [Presentation] "Is the recognition of cognate antigens always required for the determination of the tissue specificity of autoimmune diseases associated with MHC II? Symposium 11" New Aspect of Effector T cell Functions2 (2009)
  • Author(s): Murakami M., and T. Hirano
  • Organizer: The 39t Annual Meeting of The Japanese Society for Immunology
  • Place of Presentation: Osaka I nternational Convention Center, Osaka, Japan
  • Year and Date: 2009-12-04
• [Presentation] The recognition of specific antigens is not always required for the development of tissue-specific autoimmune diseases associated with MHC II (2009)
  • Author(s): Masaaki Murakami, Hideki Ogura, Yuko Okuyama, Yoichiro Iwakura, Kiyoshi Takatsu, & Toshio Hirano
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2009-12-02
• [Presentation] How does IL-17 induce Autoimmune Diseases (2009)
  • Author(s): Murakami, M
  • Organizer: The 2md International Symposium of WPI-IFReC(世界トップレベル研究拠点大阪大学免疫学フロンティア研究センター第二回国際シンポジム)
  • Place of Presentation: Osaka, Japan
  • Year and Date: 2009-02-12
• [Remarks]
  • URL: http://www.med.osaka-u.ac.jp/pub/molonc/www/index.htm1
• [Patent(Industrial Property Rights)] IL-6アンプの形成を正か負に制御して慢性炎症性疾患を制御する分子郡の発明 (2011)
  • Inventor(s): 平野俊夫、村上正晃
  • Industrial Property Rights Holder: 国立大学法人大阪大学
  • Industrial Property Number: 届出受付番号K20110052(K20110053を併合)
  • Filing Date: 20110000
• [Patent(Industrial Property Rights)] IL-6アンプの形成を正か負に制御して慢性炎症性疾患を制御する分子郡の発明 (2011)
  • Inventor(s): 平野俊夫、村上正晃平野俊夫、村上正晃
  • Industrial Property Rights Holder: 国立大学法人大阪大学
  • Industrial Property Number: PCT/ JP2011/ 071022
  • Filing Date: 2011-09-14