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

• 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
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 免疫学 / 細胞動員 / 血管内皮細胞 / 自然免疫 / 獲得免疫 / 血管内細胞

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
  • Journal Title: J Immunol. Volume: 190 Pages: 2036-2048
  • 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: 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 Science Volume: 103 Pages: 1460-1466
  • 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.
  • Journal Title: Journal of Immunology Volume: 189 Pages: 191-199
  • 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: Biochemical and Biophysical Research Communications Volume: 406 Pages: 649-655
  • DOI: 10.1016/j.bbrc.2011.02.135
  • Peer Reviewed
• [Journal Article] TIM-3 is a promising target to selec tively kill acute myeloid leukemia s tem cells (2010)
  • Author(s): Kikushige Y, Shima T 他7名
  • Journal Title: Cell Stem Cell Volume: 7巻 Pages: 708-717
  • 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: 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: 10.1111/j.1349-7006.2009.01398.x
  • NAID: 10026587701
  • 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., et al
  • Journal Title: J Med Virol. Volume: 82 Pages: 1545-1553
  • Peer Reviewed
• [Journal Article] A LIM domain-containing adaptor, leupaxin, localizes in focal adhesion and suppresses the integrin-induced tyrosine phosphorylation of paxillin. (2010)
  • Author(s): Tanaka, T., et al
  • Journal Title: Cancer Sci. Volume: 101 Pages: 363-368
  • NAID: 10026587701
  • 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] The autotaxin/lysophosphatidic acid axis regulates lymphocyte extravasation at lymph node high endothelial venules (2012)
  • Author(s): Bai, Z., et al
  • Organizer: Keystone Symposia Conference on Chemokines and Leukocyte Trafficking
  • Place of Presentation: Colorado
  • 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] Constitutive pDC migration to the splenic white pulp is cooperatively regulated by CCR7 ligands and CXCL12 (2011)
  • Author(s): Umemoto, E., et al
  • Organizer: The 40th 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
• [Presentation] Nepmucin mediates uptake of apoptotic cells in the endothelial cells of high endothelial venules. (2010)
  • Author(s): Umemoto, E., et al
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: Kobe
  • Year and Date: 2010-08-24
• [Presentation] The study of mesothelioma cancer stem cells using in vivo proliferation and sphere culture models.
  • Author(s): Ohno Y.
  • Organizer: The 21st Annual Meeting of the Japanese Cancer Association for Metastasis Research
  • Place of Presentation: オリエンタルホテル広島（ 広島市 ）
• [Presentation] Stem cell-like properties in CD133+ cells isolated from xenografted human malignant mesothelioma in immunodeficient mice.
  • Author(s): Ohno Y.
  • Organizer: The 71st Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Royton Sapporo（ Sapporo ）
• [Remarks]