PILRによるCD45を介した新たなT細胞自己応答制御機構の解明

• Project/Area Number: 20060014
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Osaka University
• Principal Investigator: 荒瀬 尚 大阪大学, 微生物病研究所, 教授 (10261900)
• Co-Investigator(Kenkyū-buntansha): 末永 忠広 大阪大学, 微生物病研究所, 助教 (20396675) ; 上堀 淳二 (上掘 淳二) 大阪大学, 微生物病研究所, 助教 (20432429)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥9,400,000 (Direct Cost: ¥9,400,000); Fiscal Year 2009: ¥4,700,000 (Direct Cost: ¥4,700,000); Fiscal Year 2008: ¥4,700,000 (Direct Cost: ¥4,700,000)
• Keywords: PILR / CD45 / ペア型レセプター / 免疫制御 / T細胞 / 樹状細胞 / 免疫応答

Research Abstract

CD45は免疫細胞に発現する膜型フォスファターゼであり、リンパ球の分化増殖に重要な機能を担っている。CD45のフォスファターゼ活性化がどのように制御されているかについては長年議論が続いている。一方、T細胞の活性化に重要な機能を担う抗原提示細胞には様々な免疫制御分子が発現しており、T細胞の活性化制御に深く関わっている。我々は、抗原提示細胞に発現する免疫制御分子としてPILRを同定した。PILRは細胞内領域に抑制化シグナルを伝達するITIM配列を持った細胞表面分子である。我々はPILRの解析により、可溶型CD45が抑制化レセプターPILRに特異的に会合することを発見した。そこで、本研究では、PILRによるCD45の機能制御がT細胞の自己認識制御にどのように関与しているかを解明し、新たなT細胞自己応答制御機構を解析した。その結果、抗原提示細胞の発現するPILRがT細胞の増殖を顕著に誘導することが明らかになり、PILRによるCD45の機能制御がT細胞応答制御に重要であることが判明した。また、PILRは顆粒球に発現しており、顆粒球上のCD45とcisの相互作用をし、抑制化シグナルを伝達している可能性が明らかになった。特に、PILRの非存在下では顆粒球の遊走能が顕著に亢進しており、Erkのリン酸化も更新することが明らかになった。以上より、PILRはリガンド分子とcisまたはtransの双方の相互作用によって免疫応答を負に制御していることが明らかになった。

Research Products

• [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., 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 PILRα depends on specific sialylated O-linked glycans on gB (2009)
  • Author(s): Wang, J., Fan, F., 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., Seino, K.I.
  • Journal Title: Int.Immunol Volume: 21 Pages: 1101-1103
  • NAID: 10027389540
  • Peer Reviewed
• [Journal Article] Entry of herpes simplex virus 1 and other alphaherpesviruses via the paired immunoglobulin-like type 2 receptor α. (2009)
  • Author(s): Arii, J., Uema, M., Morimoto, T., Sagara, H., Akashi, H., Ono, E., Arase, H., Kawaguchi, Y
  • 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., Spear, P.G.
  • Journal Title: J.Virol. Volume: 83 Pages: 7384-7390
  • 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., Spear, P.G.
  • Journal Title: .Virol. 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., Kawaguchi, Y.
  • Journal Title: J.Virol. 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., Lanier, L.L.
  • Journal Title: J.Exp.Med. 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., Kamogawa-Schifter, Y.
  • Journal Title: Eur.J.Immunol. 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., Horuzsko, A.
  • Journal Title: Proc.Natl.Acad.Sci.USA. 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., Kikutani, H.
  • Journal Title: Int.Immunol. 20 Pages: 695-708
  • NAID: 10021241281
  • Peer Reviewed
• [Journal Article] PILRα is 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., Arase, H.
  • Journal Title: Cell 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., Maenaka, K.
  • Journal Title: J.Biol.Chem. 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., Arase, H.
  • Journal Title: J.Immunol. 180 Pages: 1686-1693
  • Peer Reviewed
• [Journal Article] xpression, crystallization and preliminary x-ray diffraction analysis of human paired Ig-like type 2 receptor α(PILRα). (2008)
  • Author(s): Tabata, S., Kuroki, K., Maita, N., Wang, J., Shiratori, I., Arase, H., Kohda, D., Maenaka, K.
  • Journal Title: J.Immunol. 64 Pages: 44-46
  • Peer Reviewed
• [Presentation] ペア型レセプターを介したヘルペスウィルス感染制御機構 (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(招待講演)
  • Year and Date: 2010-01-18
• [Presentation] Regulation of herpesvirus infection by paired receptors (2009)
  • Author(s): Hisashi Arase
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪市(招待講演)
  • Year and Date: 2009-12-02
• [Presentation] Immune Evasion of Varicella-Zoster Virus (VZV) via Siglec-7 (2009)
  • Author(s): Tadahiro Suenaga, Fuminori Arisawa, 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 PILRα ligand expressed in the brain (2009)
  • Author(s): 木檜周、白鳥行大、王静、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] 水痘帯状庖疹ウィルス(VZV)の新規エントリーレセプター (2009)
  • Author(s): 末永忠広、有澤史倫、佐藤毅史、Pranee Somboonthum、森康子、荒瀬尚
  • Organizer: 第57回日本ウィルス学会
  • 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): 木檜周、大道寺智、上田真世、中屋隆明、荒瀬尚
  • Organizer: 第57回日本ウィルス学会学術集会
  • 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): 山口宗親、黒木喜美子、田畑栄一、真板宣夫、梶川瑞穂、尾瀬農之、中村聖子、王静、佐藤毅、荒瀬尚、前仲勝実
  • Organizer: 第57回日本ウィルス学会・学術集会
  • 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, Takeshi Satoh, Pranee Somboonthum, Yasuko Mori, 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
  • Place of Presentation: Lucca (Barga), Italy(招待講演)
  • Year and Date: 2009-06-09
• [Presentation] Molecular basis for recognition of Paired Immunoglobulin Like type2 Receptor (PILR) α to glycoprotein B (gB) of herpes simplex virus-1 (HSV-1) (2009)
  • Author(s): YAMAGUCHI Munechika, KUROKI Kimiko, TABATA Shigekazu, MAITA Nobuo, OSE Toyoyuki, KAJIKAWA Mizuho, NAKAMURA Seiko, WANG Jing, SATOH Takeshi, ARASE Hisashi, MAENAKA Katsumi
  • Organizer: 第39回日本免疫学会総会・学術集会
  • Place of Presentation: 大阪市
• [Presentation] ペア型レセプターPILRを介した単純ヘルペスウィルス感染機構 (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] 単純ヘルペスウィ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ィルス感染機構 (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/
• [Remarks]
  • URL: http://immchem.biken.osaka-u.ac.jp