Trafficking of immune-competent cells mediated by high endothelial venule-associated cell trafficking signals and regulation of innate and acquired immune responses.

2012 Fiscal Year Final Research Report

• Project/Area Number: 22590440
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: Hyogo University of Health Sciences
• Principal Investigator: TANAKA Toshiyuki 兵庫医療大学, 薬学部, 教授 (30217054)
• Co-Investigator(Kenkyū-buntansha): UEDA Haruyasu 兵庫医療大学, 薬学部, 准教授 (10330458) ; OHNO Yoshiya 兵庫医療大学, 薬学部, 助教 (40509155)
• Project Period (FY): 2010 – 2012
• Keywords: 免疫学 / 細胞動員 / 血管内皮細胞 / 自然免疫 / 獲得免疫

Research Abstract

Trafficking of immune-competent cell is crucial for efficient linkage between innate and adaptive immune responses. High endothelial venues (HEVs) recruit lymphocyte to lymph nodes, and express various tissue-specific cell trafficking signals. In this study, we found followings; 1) lymphocyte transmigration across the basal lamina of the HEVs is regulated, at least in part, by autotaxin (ATX) and its end-product, lysophosphatidic acid (LPA), 2) plasmacytoid dendritic cells employ both CCR7 and CXCR4 as critical chemokine receptors to migrate into the splenic white pulp under steady-state conditions, and 3) endothelial cells recognized regional inflammatory status and regulate expression of cell trafficking-associated molecules.

Research Products

• [Journal Article] Constitutive lymphocyte transmigration across the basal lamina of high endothelial venules is regulated by the Autotaxin/Lysophosphatidic Acid axis. (2013)
  • Author(s): Bai Z, Cai L, Umemoto E, Takeda A, Tohya K, Komai Y, Veeraveedu PT, Hata H, Sugiura Y, Kubo A, Suematsu M, Hayasaka H,Okudaira S, Aoki J, Tanaka T, Albers HMHG, Ovaa H, Miyasaka M.
  • Journal Title: J Immunol Volume: 190 Pages: 2036-2048
  • DOI: DOI:10.4049/jimmunol.1202025
  • Peer Reviewed
• [Journal Article] Interleukin-15 plays an essential role in the pathogenesis of autoimmune diabetes in the NOD mouse. (2012)
  • Author(s): Bobbala D, Chen XL, Leblanc C, Mayhue M, Stankova J, Tanaka T, Chen YG, Ilangumaran S, Ramanathan S.
  • Journal Title: Diabetologia Volume: 55 Pages: 3010-3020
  • DOI: DOI:10.1007/s00125-012-2675-1
  • Peer Reviewed
• [Journal Article] NIH3T3 cells overexpressing CD98 heavy chain resist early G1 arrest andapoptosis induced by serum starvation. (2012)
  • Author(s): Hara K, Ueda S, Ohno Y, Tanaka T, Yagi H, Okazaki S, Kawahara R, Masayuki T, Enomoto T, Hashimoto Y, Masuko K, Masuko T.
  • Journal Title: Cancer Sci Volume: 103 Pages: 1460-1466
  • DOI: DOI:10.1111/j.1349-7006.2012.02304.x
  • Peer Reviewed
• [Journal Article] Constitutive plasmacytoid dendritic cell migration to the splenic white pulp is cooperatively regulated by CCR7- and CXCR4-mediated signaling. (2012)
  • Author(s): Umemoto E, Otani K, Ikeno T, Verjan Garcia N, Hayasaka H, Bai Z, Jang MH, Tanaka T, Nagasawa T, Ueda K, Miyasaka M.
  • Journal Title: J Immunol Volume: 189 Pages: 191-199
  • DOI: DOI:10.4049/jimmunol.1200802
  • Peer Reviewed
• [Journal Article] Oncogenicity of L-type amino-acid transporter 1 (LAT1) revealed by targeted gene disruption in chicken DT40 cells: LAT1 is a promising molecular target for human cancer therapy. (2011)
  • Author(s): Ohkawa M, Ohno Y, Masuko K, Takeuchi A, Suda K, Kubo A, Kawahara R, Okazaki S, Tanaka T, Saya H, Seki M, Enomoto T, Yagi H, Hashimoto Y, Masuko T.
  • Journal Title: Biochem Biophys Res Commun Volume: 406 Pages: 649-655
  • DOI: DOI:10.1016/j.bbrc.2011.02.135
  • Peer Reviewed
• [Journal Article] TIM-3 is a promising target to selectively kill acute myeloid leukemia stem cells. (2010)
  • Author(s): Kikushige Y, Shima T, Takayanagi S, Urata S, Miyamoto T, Iwasaki H, Takenaka K,Teshima T, Tanaka T, Inagaki Y, Akashi K.
  • Journal Title: Cell Stem Cell Volume: 7 Pages: 708-717
  • DOI: DOI:10.1016/j.stem.2010.11.014
  • Peer Reviewed
• [Journal Article] Natural killer cells target HCV core proteins during the innate immune response in HCV transgenic mice. (2010)
  • Author(s): Satoh K, Takahashi H, Matsuda C, Tanaka T, Miyasaka M, Zeniya M, Kohara M.
  • Journal Title: J Med Virol Volume: 82 Pages: 1545-1553
  • DOI: DOI:10.1002/jmv.21859
  • Peer Reviewed
• [Journal Article] LIM domain-containing adaptor, leupaxin, localizes in focal adhesion and suppresses the integrin-induced tyrosine phosphorylation of paxillin. (2010)
  • Author(s): Tanaka T, Moriwaki K, Murata S, Miyasaka M.
  • Journal Title: Cancer Sci Volume: 101 Pages: 363-368
  • DOI: DOI:10.1111/j.1349-7006.2009.01398.x
  • Peer Reviewed
• [Presentation] Stem cell-like propertiesin CD133+ cells isolated from xenografted human malignant mesothelioma in immunodeficient mice. (2012)
  • Author(s): Ohno Y, Tanaka T.
  • Organizer: The 71st Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Royton Sapporo (Sapporo)
  • Year and Date: 2012-09-19
• [Presentation] The study of mesothelioma cancer stem cells using in vivo proliferation and sphere culture models. (2012)
  • Author(s): Ohno Y, Ueda H, Tanaka T.
  • Organizer: The21st Annual Meeting of the Japanese CancerAssociation for Metastasis Research.
  • Place of Presentation: Oriental Hotel Hiroshima (Hiroshima)
  • Year and Date: 2012-07-13
• [Presentation] The autotaxin/lysophosphatidic acid axis regulates lymphocyte extravasation at lymph node high endothelial venules. (2012)
  • Author(s): Bai Z, Cai L, Umemoto E, Tohya K, Takeda A, Hata E, Hayasaka H, Tanaka T, Miyasaka M.
  • Organizer: Keystone Symposia Conference on Chemokines and Leukocyte Trafficking.
  • Place of Presentation: Colorado, USA.
  • Year and Date: 2012-01-09
• [Presentation] Constitutive pDC migration to the splenic white pulp is cooperatively regulated by CCR7 ligands and CXCL12. (2011)
  • Author(s): Umemoto E, Ikeno T, Verjan Garcia N, Hayasaka H, Bai Z, Jang, M.H, Tanaka T, Miyasaka M.
  • Organizer: The40th annual meeting of the Japanese Society for Immunology.
  • Place of Presentation: Makuhari Messe (Chiba).
  • Year and Date: 2011-11-29
• [Presentation] Nepmucin mediates uptake of apoptotic cells in the endothelial cells of high endothelial venules. (2010)
  • Author(s): Umemoto, E., Kunizawa, K., Jin, S.,Yonekura, S., Jang, M.H., Tanaka, T, Miyasaka, M.
  • Organizer: 14th International Congress of Immunology.
  • Place of Presentation: Kobe International Conference Center (Kob.
  • Year and Date: 2010-08-24
• [Remarks]
  • URL: http://www2.huhs.ac.jp/~h070015t/index. html