New immune regulatory mechanism by paired receptors

2010 Fiscal Year Final Research Report

• Project/Area Number: 20390143
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: Osaka University
• Principal Investigator: ARASE Hisashi 大阪大学, 微生物病研究所, 教授 (10261900)
• Co-Investigator(Kenkyū-buntansha): SUENAGA Tadahiro 大阪大学, 微生物病研究所, 助教 (20396675) ; UEHORI Junji 大阪大学, 微生物病研究所, 助教 (20432429)
• Project Period (FY): 2008 – 2010
• Keywords: NK細胞 / 自然免疫 / 免疫制御 / 炎症 / 獲得免疫 / 好中球

Research Abstract

In this study, we tried to elucidate host and pathogen ligands for paired receptors. By this analysis, we analyzed how immune response to self is regulated via inhibitory receptors and how pathogens evade immune response via inhibitory receptors. In addition, we analyzed how activating receptors is involved in host resistance to pathogens. We extensively analyzed function of PILR, one of paired receptors. We found that PILR associates with glycoprotein B of herpes simplex virus and is involved in entry of herpes simplex virus into cells. Furthermore, we found that specific O-glycans on CD99 and glycoprotein B are essential to associate with PILR. In addition, we identified PANP, a new molecules that is specifically expressed in nerve tissue, as a new ligand for PILR and suggested that PANP might be involved in the immune regulation in nerve tissues. These results suggested that paired receptors play an important role in immune regulation.

Research Products

• [Journal Article] PANP is a novel O-glycosylated PILRαligand expressed in neural tissues (2011)
  • Author(s): Kogure, A., Shiratori, I., Wang, J., L. Lanier, L., Arase, H.
  • Journal Title: Biochem Biophys Res Commun Volume: 405 Pages: 428-433
  • Peer Reviewed
• [Journal Article] Non-muscle myosin IIA is a functional entry receptor for herpes simplex virus-1 (2010)
  • Author(s): Arii, J., Goto, H., Suenaga, T., Oyama, M., Kozika-Hata, H., Imai, T., Minowa, A., Akashi, H., Arase, H., Kawaoka, Y., and Kawaguchi, Y.
  • Journal Title: Nature Volume: 467 Pages: 859-862
  • Peer Reviewed
• [Journal Article] A Single Amino Acid Substitution in Herpes simplex virus 1 Envelope Glycoprotein B at a Site Required for Binding to the Paired Immunoglobulin-like Type 2 Receptorα(PILRα) Abrogates PILRα-dependent Viral Entry and Reduces Pathogenesis (2010)
  • Author(s): Arii, J., Wang, J., Morimoto, T., Suenaga, T., Akashi, H., Arase, H., and Kawaguchi, Y.
  • Journal Title: J. Virol Volume: 84 Pages: 10773-10783
  • Peer Reviewed
• [Journal Article] Myelin-associated glycoprotein mediates membrane fusion and entry of neurotropic herpesviruses (2010)
  • Author(s): Suenaga, T., Satoh, T., Somboonthum, P., Kawaguchi, Y., Mori, Y., and Arase, H.
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 107 Pages: 866-871
  • Peer Reviewed
• [Journal Article] Binding and uptake of H-ferritin are mediated by human transferrin receptor-1 (2010)
  • Author(s): Li, L., Fang, C. J., Ryan, J. C., Niemi, E. C., Lebron, J. A., Bjorkman, P. J., Arase, H., Torti, F. M., Torti, S. V., Nakamura, M. C., Seaman, W. E.
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 107 Pages: 3505-3510
  • Peer Reviewed
• [Journal Article] Binding of herpes simplex virus glycoprotein B(gB) to PILRαdepends on specific sialylated O-linked glycans on gB (2009)
  • Author(s): Wang, J., Fan, Q., Satoh, T., Arii, J., Lanier, L. L., Spear, P. G., Kawaguchi, Y., Arase, H.
  • Journal Title: J. Virol Volume: 83 Pages: 13042-13045
  • Peer Reviewed
• [Journal Article] The study of regulatory T cells and NKT cells in Japan : a historical perspective (2009)
  • Author(s): Arase, H., and Seino, K. I.
  • Journal Title: Int. Immunol Volume: 21 Pages: 1101-1103
  • Peer Reviewed
• [Journal Article] and Kawaguchi, Y. Entry of herpes simplex virus 1 and other alphaherpesviruses via the paired immunoglobulin-like type 2 receptorα (2009)
  • Author(s): Arii, J., Uema, M., Morimoto, T., Sagara, H., Akashi, H., Ono, E., Arase, H.
  • Journal Title: J. Virol Volume: 83 Pages: 4520-4527
  • Peer Reviewed
• [Journal Article] Differential effects on cell fusion activity of mutations in herpes simplex virus 1 glycoprotein B(gB) dependent on whether a gD receptor or a gB receptor is overexpressed (2009)
  • Author(s): Fan, Q., Lin, E., Satoh, T., Arase, H., and Spear, P. G.
  • Journal Title: J. Virol. Volume: 83 Pages: 7384-7390
  • Peer Reviewed
• [Journal Article] Herpes simplex virus 1 protein kinase Us3 phosphorylates viral envelope glycoprotein B and regulates its expression on the cell surface (2009)
  • Author(s): Kato, A., Arii, J., Shiratori, I., Akashi, H., Arase, H., and Kawaguchi, Y.
  • Journal Title: J. Virol Volume: 83 Pages: 250-261
  • Peer Reviewed
• [Journal Article] Ly49H signaling through DAP10 is essential for optimal natural killer cell responses to mouse cytomegalovirus infection (2009)
  • Author(s): Orr, M. T., Sun, J. C., Hesslein, D. G., Arase, H., Phillips, J. H., Takai, T., and Lanier, L. L.
  • Journal Title: J. Exp. Med Volume: 206 Pages: 807-817
  • Peer Reviewed
• [Journal Article] Ly49Q ligand expressed by activated B cells induces plasmacytoid DC maturation (2009)
  • Author(s): Toma-Hirano, M., Namiki, S., Shibata, Y., Ishida, K., Arase, H., Miyatake, S., Arai, K., and Kamogawa-Schifter, Y.
  • Journal Title: Eur. J. Immunol Volume: 39 Pages: 1344-1352
  • Peer Reviewed
• [Journal Article] Modulation of dendritic cell differentiation by HLA-G and ILT4 requires the IL-6-STAT3 signaling pathway (2008)
  • Author(s): Liang, S., Ristich, V., Arase, H., Dausset, J., Carosella, E. D. and Horuzsko, A.
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 105 Pages: 8357-8362
  • Peer Reviewed
• [Journal Article] Bimodal regulation of T cell-mediated immune responses by TIM-4 (2008)
  • Author(s): Mizui, M., Shikina, T., Arase, H., Suzuki, K., Yasui, T., Rennert, P. D., Kumanogoh, A., and Kikutani, H.
  • Journal Title: Int. Immunol Volume: 20 Pages: 695-708
  • Peer Reviewed
• [Journal Article] PILRαis a herpes simplex virus-1 entry co-receptor that associates with glycoprotein B (2008)
  • Author(s): Satoh, T., Arii, J., Suenaga, T., Wang, J., Kogure, A., Uehori, J., Arase, N., Shiratori, I., Tanaka, S., Kawaguchi, Y., Spear, P. G., Lanier, L. L. and Arase, H.
  • Journal Title: Cell Volume: 132 Pages: 935-944
  • Peer Reviewed
• [Journal Article] Biophysical characterization of O-glycosylated CD99 recognition by paired Ig-like type 2 receptors(PILR) (2008)
  • Author(s): Tabata, S., Kuroki, K., Wang, J., Kajikawa, M., Shiratori, I., Kohda, D., Arase, H. and Maenaka, K.
  • Journal Title: J. Biol. Chem Volume: 283 Pages: 8893-8901
  • Peer Reviewed
• [Journal Article] An essential role of sialylated O-linked sugar chains in the recognition of mouse CD99 by paired immunoglobulin-like type 2 receptor(PILR) (2008)
  • Author(s): Wang, J., Shiratori, I., Satoh, T., Lanier, L. L., and Arase, H.
  • Journal Title: J. Immunol Volume: 180 Pages: 1686-1693
  • Peer Reviewed
• [Presentation] 神経組織指向性αヘルペスウイルスのエントリーレセプター (2010)
  • Author(s): 末永忠広, 荒瀬尚
  • Organizer: 第58回日本ウイルス学会学術集会
  • Place of Presentation: 徳島県郷土文化会館(徳島市)
  • Year and Date: 2010-11-09
• [Presentation] Crucial Role of Sialic Acid Binding Receptors in Herpes Virus Infection (2010)
  • Author(s): Hisashi Arase
  • Organizer: Annual Conference of the Society for Glycobiology
  • Place of Presentation: St. Pete Beach, FL(USA)
  • Year and Date: 2010-11-08
• [Presentation] Regulation of herpesvirus infection by paired receptors (2010)
  • Author(s): Hisashi Arase
  • Organizer: The CSI-IFReC Joint Symposium on Immunology
  • Place of Presentation: Hangzhou(China)
  • Year and Date: 2010-11-03
• [Presentation] Interaction between Siglec and Varicella-Zoster Virus(VZV) (2010)
  • Author(s): Tadahiro Suenaga
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: 神戸国際展示場(神戸市)
  • Year and Date: 2010-08-24
• [Presentation] Myelin-Associated Glycoprotein Associates with gB and is Involved in Membrane Fusion during Neurotropic Herpesvirus Infection (2010)
  • Author(s): Tadahiro Suenaga
  • Organizer: 35th International Herpesvirus Workshop
  • Place of Presentation: Salt Lake City, Utah(USA)
  • Year and Date: 2010-07-25
• [Presentation] Crucial role of glycan binding receptors in herpesvirus infection (2010)
  • Author(s): Hisashi Arase
  • Organizer: 1st Asia Pacific Workshop
  • Place of Presentation: Seoul,(Korea)
  • Year and Date: 2010-07-16
• [Presentation] 新規神経指向性ヘルペスウイルスレセプタ-の同定と解析 (2010)
  • Author(s): 末永忠広、荒瀬尚
  • Organizer: 第51回日本神経学会総会
  • Place of Presentation: 東京国際フォーラム(東京)
  • Year and Date: 2010-05-21
• [Presentation] ペア型レセプターを介したヘルペスウイルス感染制御機構 (2010)
  • Author(s): 荒瀬尚
  • Organizer: 日本食品免疫学会次世代シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2010-01-08
• [Presentation] Regulation of herpesvirus infection by paired receptors (2009)
  • Author(s): 荒瀬尚
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪市
  • Year and Date: 2009-12-02
• [Presentation] Molecular basis for recognition of Paired Immunoglobulin Like type2 Receptor(PILR)αto glycoprotein B(gB) of herpes simplex virus-1(HSV-1) (2009)
  • Author(s): ARASE Hisashi
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪市
  • Year and Date: 2009-12-02
• [Presentation] Immune Evasion of Varicella-Zoster Virus(VZV) via Siglec-7 (2009)
  • Author(s): Tadahiro Suenaga, Hisashi Arase
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪市
  • Year and Date: 2009-12-02
• [Presentation] PILR-L2 is a novel PILRαligand expressed in the brain (2009)
  • Author(s): 荒瀬尚
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪市
  • Year and Date: 2009-12-02
• [Presentation] 水痘帯状疱疹ウィルス(VZV)の新規エントリーレセプター (2009)
  • Author(s): 末永忠広, 荒瀬尚
  • Organizer: 第57回日本ウイルス学会
  • Place of Presentation: 東京
  • Year and Date: 2009-10-26
• [Presentation] Hemopexinによる新たなインフルエンザ感染防御機構 (2009)
  • Author(s): 荒瀬尚
  • Organizer: 第57回日本ウイルス学会
  • Place of Presentation: 東京
  • Year and Date: 2009-10-26
• [Presentation] Paired Immunoglobulin(Ig) Like type 2 Receptor(PILR)αによるGlycoprotein B(gB)認識機構の解明 (2009)
  • Author(s): 荒瀬尚
  • Organizer: 第57回日本ウイルス学会
  • Place of Presentation: 東京
  • Year and Date: 2009-10-26
• [Presentation] A Varicells-Zoster Virus entry receptor that mediates membrane fusion and infection (2009)
  • Author(s): Tadahiro Suenaga, Hisashi Arase
  • Organizer: 14th International Conference on Immunobiology and Prophylaxis of Human Herpesvirus
  • Place of Presentation: Kobe
  • Year and Date: 2009-10-06
• [Presentation] Regulation of herpesvirus infection by paired receptors (2009)
  • Author(s): Hisashi Arase
  • Organizer: The Viruses and Cells Gordon Conference
  • Year and Date: 2009-06-09
• [Presentation] ペア型レセプターPILRを介した単純ヘルペスウイルス感染機構 (2008)
  • Author(s): 荒瀬尚
  • Organizer: 日本分子生物学会シンポジウム
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-12
• [Presentation] 単純ヘルペスウイルス感染におけるエンベロープのO型糖鎖修飾の機能 (2008)
  • Author(s): 荒瀬尚
  • Organizer: 日本糖鎖科学コンソーシアムシンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2008-12-04
• [Presentation] 抑制化レセプターPILRを介した単純ヘルペスウイルス感染機構 (2008)
  • Author(s): 荒瀬尚
  • Organizer: 日本生体防御学会学術総会シンポジウム
  • Place of Presentation: 札幌
  • Year and Date: 2008-07-10
• [Remarks]
  • URL: http://immchem.biken.osaka-u.ac.jp/