Elucidation of novel immune regulatory mechanism by PILR that belongs to NK cell receptor family.

• Project/Area Number: 18390151
• 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 Osaka University, Research Institute for Microbial Diseases, Professor (10261900)
• Project Period (FY): 2006 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥16,830,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥2,130,000); Fiscal Year 2007: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000); Fiscal Year 2006: ¥7,600,000 (Direct Cost: ¥7,600,000)
• Keywords: PILR / CD45 / Paired receptors / NK cell / Immune regulation / NK細胞レセプター / 免疫逃避 / 単純ヘルペスウィルス

Research Abstract

In this study, we have analyzed how PILR, one of NK cell receptor family molecules, is involved in immune system. Especially, we have analyzed how PILR regulates innate immune response and acquired immune response. Furthermore, we have tried to develop a method to regulate allergic diseases and autoimmune diseases by regulating interaction between PILR and PILR ligands. When we have analyzed expression of PILR ligands and function of the ligands, we have found that PILR recognizes CD45 expressed on CD8 T cells. Furthermore, we analyzed the function of the interaction between PILR and CD45, by stimulating T cells with anti-CD3 mAb and PILR-Ig fusion protein. From these analyses, we found that the interaction significantly augment the response of CD8 T cells. Furthermore, PILR expressed on antigen presenting cells significantly augmented the response of T cells. In summary, PILR was revealed to regulate CD8 T cell activation by interacting with CD45 expressed on CD8 T cells. Development of methods to regulate interaction between CD45 and PILR seems to be involved in the development of methods to regulate allergic diseases and autoimmune diseases. Therefore, further analyses of the function of PILR seem to be important to elucidate the mechanism of immune regulation.

Research Products

• [Journal Article] PILR α 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
  • Description: 「研究成果報告書概要(和文)」より
  • 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
  • Description: 「研究成果報告書概要(和文)」より
  • 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
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Expression, crystallization and preliminary x-ray diffraction analysis of human paired Ig-like type 2 receptor α (PILR α) (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
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] PILRα is a herpes simplex virus-1 entry coreceptor that associates with glycoprotein B. (2008)
  • Author(s): Satoh, T., Am, 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
  • Description: 「研究成果報告書概要(欧文)」より
• [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
  • Description: 「研究成果報告書概要(欧文)」より
• [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: 8893-89001
  • Description: 「研究成果報告書概要(欧文)」より
• [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
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Expression, crystallization and preliminary X-ray diffraction analysis of human paired Ig-like type 2 receptor alpha (PILRα). (2008)
  • Author(s): Tabata, S., Kuroki, K., Maita, N., Wang, J., Shiratori, I., Arase, H., Kohda, D., Maenaka, K.
  • Journal Title: Ada Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 64 Pages: 44-46
  • Description: 「研究成果報告書概要(欧文)」より
• [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 (In press)
  • 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. (In press)
  • Peer Reviewed
• [Journal Article] An essential role of sialylated O-linked sugar chains in the recognition of mouse CD99 by paired immunolobulin-like type 2 recefor (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] Expression, 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
• [Journal Article] Cloning of B-cell-specific tetramembrane spanning molecule BTS possessing B cell proliferation inhibitory function. (2007)
  • Author(s): Suenaga, T., Arase, H., Yamasaki, S., Kohno, M., Yokosuka, T., Takeuchi, A., Hattori, T., Saito, T.
  • Journal Title: Eur. J. Immunol. 37 Pages: 3197-3207
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Structural elucidation of the m157 mouse cytomegalovirus ligand for Ly49 natural killer cell receptors. (2007)
  • Author(s): Adams, E. J., Juo, Z. S., Venook, E. T., Boulanger, M. J., Arase, H., Lanier, L. L., Garcia, K. C.
  • Journal Title: Proc. Natl. Acad. Sci. USA. 104 Pages: 10128-10133
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] KIR3DS1, a Gene Implicated in Resistance to Progression to AIDS, Encodes a DAP12-Associated Receptor Expressed on NK Cells That Triggers NK Cell Activation. (2007)
  • Author(s): Carr H. William
  • Journal Title: J. Immunol. 178 Pages: 647-651
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Cloning of B-cell-specific tetramembrane spanning molecule BTS possessing B cell proliferation inhibitory function (2007)
  • Author(s): Suenaga, T, Arase. H., Yamasaki, S., Kohno, M., Yokosuka, T., Takeuchi, A., Hattori, T., Saito, T.
  • Journal Title: Eur. J. Immunol. 37 Pages: 3197-3207
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Structural elucidation of the ml57 mouse cytomegalovirus ligand for Ly49 natural killer cell receptors. (2007)
  • Author(s): Adams, E. J., Juo, Z. S., Venook, R. T., Boulanger, M. J., Arase. H., Lanier, L. L., Garcia K. C.
  • Journal Title: Proc. Natl. Acad. Sci. USA. 104 Pages: 10128-10133
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] KIR3DS1, a gene implicated in resistance to progression to AIDS, encodes a DAP12-associated receptor expressed on NK cells that triggers NK cell activation. (2007)
  • Author(s): Carr, W. H., Rosen, D. B., Arase. H., Nixon, D. F., Michaelsson, J., Lanier, L. L.
  • Journal Title: J. Immunol. 178 Pages: 647-651
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Cloning of B-cell-specific tetramembrane spanning molecule BTS possessing B cell proliferation inhibitory function (2007)
  • Author(s): Suenaga, T., Arase, H., Yamasaki, S., Kohno, M., Yokosuka, T., Takeuchi, A., Hattori, T., Saito, T.
  • Journal Title: Eur. J. Immunol. 37 Pages: 3197-3207
  • Peer Reviewed
• [Journal Article] Structural elucidation of the m157 mouse cytomegalovirus ligand for Ly49 natural killer cell receptors (2007)
  • Author(s): Adams, E. J., Juo, Z. S., Venook, R. T., Boulanger, M. J., Arase, H., Lanier, L. L., Garcia, K. C.
  • Journal Title: Proc. Natl. Acad. Sci. USA. 104 Pages: 10128-10133
  • Peer Reviewed
• [Journal Article] KIR3DSl, a Gene Implicated in Resistance to Progression to AIDS, Encodes a DAP12-Associated Receptor Expressed on NK Cells That Triggers NK Cell Activation. (2007)
  • Author(s): Carr H. William
  • Journal Title: J. Immunol. 178・2 Pages: 647-651
• [Journal Article] Efficient leukocyte Ig-like receptor signaling and crystal structure of disulfide-linked HLA-G dimer. (2006)
  • Author(s): Shiroishi Mitsunori
  • Journal Title: J. Biol. Chem. 281 Pages: 10439-10447
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Efficient leukocyte IG-like receptor signaling and crystal structure of disulfide-linked HLA-G dimer. (2006)
  • Author(s): Shiroishi, M., Kuroki, K., Ose, T., Rasubala, L., Shiratori, I., Arase. H., Tsumoto, K., Kumagai, I., Kohda, D., Maenaka, K.
  • Journal Title: J. Biol. Chem. 281 Pages: 10439-10447
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Efficient leukocyte Ig-like receptor signaling and crystal structure of disulfide-linked HLA-G dimer. (2006)
  • Author(s): Shiroishi Mitsunori
  • Journal Title: J. Biol. Chem. 281・15 Pages: 10439-10447
• [Presentation] Self and non-self recognition by inhibitory PILR (2007)
  • Author(s): Hisashi Arase
  • Organizer: 日本免疫学会総会シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2007-11-22
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Self and non-self recognition by inhibitory PILR (2007)
  • Author(s): Hisashi Arase
  • Organizer: Tokyo Annual Meeting of the Japanese Society for Immunology
  • Year and Date: 2007-11-22
  • Description: 「研究成果報告書概要(欧文)」より
• [Remarks] 「研究成果報告書概要(和文)」より
  • URL: http://immchem.biken.osaka-u.ac.jp/
• [Remarks]
  • URL: http://immchem.biken.osaka-u.ac.jp/
• [Patent(Industrial Property Rights)] ヘルペスウィルス感染阻害剤、ヘルペスウィルスの感染阻害方法およびその利用 (2007)
  • Inventor(s): 荒瀬尚, 佐藤毅史, 川口寧
  • Industrial Property Rights Holder: 荒瀬尚, 佐藤毅史, 川口寧
  • Industrial Property Number: 2007-005229
  • Filing Date: 2007-01-12
  • Description: 「研究成果報告書概要(和文)」より
• [Patent(Industrial Property Rights)] PILRαと結合するポリペプチド、およびそれをコードするポリヌクレオチド、並びにその利用 (2007)
  • Inventor(s): 荒瀬尚, 白鳥行大, 前仲勝実
  • Industrial Property Rights Holder: 荒瀬尚, 白鳥行大, 前仲勝実
  • Filing Date: 2007-02-27
  • Description: 「研究成果報告書概要(和文)」より
  • Overseas
• [Patent(Industrial Property Rights)] ヘルペスウィルス感染阻害剤、ヘルペスウィルスの感染阻害方法およびその利用 (2007)
  • Inventor(s): 荒瀬 尚, 佐藤毅史, 川口寧
  • Industrial Property Rights Holder: 荒瀬 尚, 佐藤毅史, 川口寧
  • Industrial Property Number: 2007-005229
  • Filing Date: 2007-01-12
• [Patent(Industrial Property Rights)] PILRαと結合するポリペプチド、およびそれをコードするポリヌクレオチド、並びにその利用 (2007)
  • Inventor(s): 荒瀬尚, 白鳥行大, 前仲勝実
  • Industrial Property Rights Holder: 荒瀬尚, 白鳥行大, 前仲勝実
  • Filing Date: 2007-02-27