Regeneration of immune severance system by the repertoire regulation

2006 Fiscal Year Final Research Report Summary

• Project/Area Number: 15078102
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: RIKEN (2004-2006); Tokyo University of Science (2003)
• Principal Investigator: KUBO Masato Kubo Laboratory for Signal Network, Research Center for Allergy and Immunology (RCAI), RIKEN Yokohama Institute, シグナル・ネットワーク研究チーム, チームリーダー (40277281)
• Project Period (FY): 2003 – 2006
• Keywords: Cytokine / Suppression / Signal / septic peritonitis / liver injury / T cell

Research Abstract

Cytokine regulate the survival, proliferation, differentiation and function of immune cells as well as cells from most other organ systems. Many of these cytokines induce the expression of SOCS proteins, a feedback inhibitor of JAK kinase. It still remains unclear how cytokine signaling regulates immune homeostasis. In this year, we studied a role of SOCS5 in septic peritonitis, and demonstrate that overexpression of SOCS5 in T cells augments innate immunity during septic peritonitis induced by cecal ligation and puncture (CLP). We also studied the role of SOCS proteins in acetaminophen (APAP)-induced acute liver injury. We demonstrate that forced expression of SOCS3 in T cells exacerbates APAP-hepatotoxicity, indicating that novel sight of SOCS3 function in innate immunity. In order to study naive and memory T cell development in the attenuated cytokine signaling, we generated the T cell specific SOCS1 transgenic lines (SOCS1Tg), and we demonstrated that the cytokine signalings was essential for survival of naive CD4 T cells in the periphery. These data demonstrated that SOCS proteins are key physiological regulators of both innate and adaptive immunity. These molecules positively and negatively regulate macrophage and dendritic-cell activation and are essential for T-cell development and differentiation. We recently reviewed these studies on SOCS proteins and their role in immunity (Nature Review Immunology).

Research Products

• [Journal Article] The role of IL-7/STAT5 pathway and suppressor of cytokine signaling 1 in maintenance of naive and memory CD4 T cells in peripheral lymphoid organs. (2007)
  • Author(s): Seki, Y, Yang, J, Okamoto, M, Tanaka, S, Goizuka, R, Farrar, M, A, Kubo, M.
  • Journal Title: The Journal of Immunology 1,178(1) Pages: 262-270
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Role of endogenous inhibitors of cytokine signaling in allergic asthma. (2007)
  • Author(s): Inoue, H, Fukuyama, S, Kubo, M, Yoshimura, A.
  • Journal Title: Current Medicinal Chemistry 14 Pages: 181-189
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Overexpression of Suppressor of Cytokine Signaling-3 in T cells Exacerbates Acetaminopheninduced Hepatotoxicity. (2007)
  • Author(s): Numata K, Kubo, M, Watanabe, H, Takagi, K, Mizuta, H, Okada, S, Ito, T, Matsukawa, A
  • Journal Title: The Journal of Immunology 178 Pages: 3777-3785
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Involvement of the Programmed Death-1/Programmed Death-1 Ligand Pathway in CD4-CD25-Regulatory T-Cell Activity to Suppress Alloimmune Responses (2007)
  • Author(s): Kitazawa, Y, Fujino, M, Wang, Q, Kimura, H, Azuma, M, Kubo, M, Abe, R, Li, X-K.
  • Journal Title: Transplantation 83 Pages: 774-782
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] SOCS proteins, cytokine signalling and immune regulation. (2007)
  • Author(s): Yoshimura, A, Naka, T, Kubo, M.
  • Journal Title: Nature Review Immunology (in press)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The role of IL-7/STAT5 pathway and suppressor of cytokine signaling 1 in maintenance of naive and memory CD4 T cells in peripheral lymphoid organs. (2007)
  • Author(s): Seki, Y., Yang, J., Okamoto, M., Tanaka, S., Goizuka, Farrar, M.A., R., Kubo, M.
  • Journal Title: J. Immunol. 1;178(1) Pages: 262-70
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Role of endogenous inhibitors of cytokine signaling in allergic asthma, (2007)
  • Author(s): Inoue, H., Fukuyama, S., Kubo, M., Yoshimura, A.
  • Journal Title: Cur. Med. Chem. 14 Pages: 181-189
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Overexpression of Suppressor of Cytokine Signaling-3 in T cells Exacerbates Acetaminophen-induced Hepatotoxicity. (2007)
  • Author(s): Numata, K., Kubo, M., Watanabe, H., Takagi, K., Mizuta, H., Okada, S., Ito, T., Matsukawa, A.
  • Journal Title: J. Immunol. 178 Pages: 3777-3785
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Involvement of the Programmed Death-1/Programmed Death-1 Ligand Pathway in CD4-CD25- Regulatory T-Cell Activity to Suppress Alloimmune Responses (2007)
  • Author(s): Kitazawa, Y., Fujino, M., Wang, Q., Kimura, H., Azuma, M., Kubo, M., Abe, R., Li, X-K.
  • Journal Title: Transplantation 83 Pages: 774-782
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] SOCS proteins, cytokine signalling and immune regulation. (2007)
  • Author(s): Yoshimura, A., Naka, T., Kubo, M.
  • Journal Title: Nature Review Immunology
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Computer Simulation of the Role of SOCS Family Protein in THelper Cell Differentiation. (2006)
  • Author(s): Yamada, S, Tsukada, J, Yoshimura, A, Kubo, M.
  • Journal Title: international lmmunology 18 Pages: 335-345
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Activation of the arylhydrocarbon receptor in the thymocytes induces thymocyte reduction independently of Fas/Fas ligand signaling pathway. (2006)
  • Author(s): Nagai, H, Kubo, M, Abe, R, Yamamoto, M, Nohara, K.
  • Journal Title: International Immunopharmacology 6 Pages: 276-286
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Suppressor of Cytokine Signaling 3 (SOCS3) in the Th2 cells evokes Th2 cytokines, lgE and eosinophilia. (2006)
  • Author(s): Kubo, M, Inoue, H.
  • Journal Title: Current Allergy and Asthma Reports 9 Pages: 32-39
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Suppressor of cytokine signaling-1 in lymphocytes regulates development of experimental colitis and inflammatory bowel disease (2006)
  • Author(s): Inagaki-Ohara K, Sasaki, A, Matsuzaki, G, Ikeda, T, Sakamoto, Y, Hotokezaka, M, Chijiiwa, K, Nawa, Y, Kubo, M, Yoshida, H, Yoshimura A.
  • Journal Title: Gut 55 Pages: 212-219
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Contribution of interleukin-18 to atopic dernatutus-like skin inflammation induced by staphylococcus aureus product in mice (2006)
  • Author(s): Terada, M, Tsutsui, H, Imai, Y, Yasuda, K, Mizutani, H, Yamanishi, K, Kubo, M, Matsui, K, Sano, H, Nakanishi, K.
  • Journal Title: Proc. Natl. Acad. Sci. USA 103 Pages: 8816-8821
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The interleukin-4 (IL-4) ebgabcer CNS-2 is regulated by Notch/RBP-J signals and controls initial IL-4 expression in NKT cells and memory-type CD4 T cells. (2006)
  • Author(s): Tanaka, S, Tsukada, J, Suzuki, W, Hayashi, K, Tanigaki, K, Tsuji, M, Honjo, T, Kubo, M.
  • Journal Title: Immunity 24 Pages: 689-701
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Role of suppressor of cytokine signaling in ocularallergy. (2006)
  • Author(s): Kubo, M, Ozaki, A, Tanaka, S, Okamoto, M, Fukushima, A.
  • Journal Title: Current Opinion in Allergy ＆ Clinical Immunology 6 Pages: 361-366
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Overexpression of Suppressor of cytokine signaling-5 in T cells augments innate immunity during septic peritonitis. (2006)
  • Author(s): Watanabe, H, Kubo, M, Numata, K, Takagi, K, Mizuta, H, Okada, S, Ito, T, Matsukawa, A.
  • Journal Title: The Journal of Immunology 15,177(12) Pages: 8650-8657
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Computer Simulation of the Role of SOCS Family Protein in T Helper Cell Differentiation. (2006)
  • Author(s): Yamada, S., Tsukada, J., Yoshimura, A, Kubo, M.
  • Journal Title: Int. Immunol. 18 Pages: 335-345
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Activation of the aryl hydrocarbon receptor in the thymocytes induces thymocyte reduction independently of Fas/Fas ligand signaling pathway. (2006)
  • Author(s): Nagai, H., Kubo, M., Ryo Abe, R., Yamamoto, M., Nohara., K.
  • Journal Title: International Immunop.harmacology 6 Pages: 276-286
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Suppressor of Cytokine Signaling 3 (SOCS3) in the Th2 cells evokes Th2 cytokines, IgE and eosinophilia (2006)
  • Author(s): Kubo, M., Inoue, H.
  • Journal Title: Current Allergy and Asthma Reports 9 Pages: 32-39
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Suppressor of cytokine signaling-1 in lymphocytes regulates development of experimental colitis and inflammatory bowel disease (2006)
  • Author(s): Inagaki-Ohara, K., Sasaki, A., Matsuzaki, G., Ikeda, T., Sakamoto, Y., Hotokezaka, M., Chijiiwa, K., Nawa, Y., Kubo, M., Yoshida, H., Yoshimura A.
  • Journal Title: Gut 55 Pages: 212-219
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Contribution of interleukin-18 to atopic dermatitis-like skin inflammation induced by Staphylococcus aureus product in mice. (2006)
  • Author(s): Terada, M., Tsutsui, H., Imai, Y., Yasuda, K., Mizutani, H., Yamanishi, K., Kubo, M., Matsui, K., Sano, H., Nakanishi, K.
  • Journal Title: Proc. Natl. Acad. Sci. USA 103 Pages: 8816-8821
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The interleukin-4 (IL-4) enhancer CNS-2 is regulated by Notch/RBP-J signals and controls initial IL-4 expression in NKT cells and memory-type CD4 T cells. (2006)
  • Author(s): Tanaka, S., Tsukada, J., Suzuki, W., Hayashi, K., Tanigaki, K., Tsuji, M., Honjo, T., Kubo, M.
  • Journal Title: Immunity 24 Pages: 689-701
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Role of suppressor of cytokine signaling in ocular allergy. (2006)
  • Author(s): Kubo, M, Ozaki, A., Tanaka, S., Okamoto, M., Fukushima, A.
  • Journal Title: Cur. Opin. Alter. Clin. Immunol. 6 Pages: 361-366
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Overexpression of Suppressor of cytokine signaling-5 in T cells augments innate immunity during septic peritonitis. (2006)
  • Author(s): Watanabe, H., Kubo, M., Numata, K., Takagi, K., Mizuta, H., Okada, S., Ito, T., Matsukawa, A.
  • Journal Title: J. Immunol. 15;177(12) Pages: 8650-8657
  • Description: 「研究成果報告書概要(欧文)」より