Elucidation of the mechanism underlying immune cell trafficking dependent on lysophospholipid signaling

• Project/Area Number: 21390151
• 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: MIYASAKA Masayuki 大阪大学, 医学系研究科, 教授 (50064613)
• Co-Investigator(Kenkyū-buntansha): HAYASAKA Haruko 大阪大学, 医学系・研究科, 助教 (70379246) ; UMEMOTO Eiji 大阪大学, 医学系・研究科, 助教 (90452440) ; BAI Zhongbin 大阪大学, 免疫学フロンティア研究センター, 特任助教(常勤) (10512840) ; VERJAN GARCIA Noel 大阪大学, 免疫学フロンティア研究センター, 特任研究員(常勤) (90533216) ; CAI Linjun 大阪大学, 免疫学フロンティア研究センター, 特任研究員(常勤) (90584079)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000); Fiscal Year 2011: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2010: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2009: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
• Keywords: リンパ球ホーミング / 血管内皮細胞 / リゾリン脂質 / 細胞接着 / ケモカイン

Research Abstract

We analyzed the role of a lysophospholipase D, autotaxin(ATX), which produces a bioactive lipid mediator, lysophospholipid(LPA). ATX is highly expressed in the high endothelial venules(HEVs) that mediate lymphocyte trafficking into lymph nodes. We found that ATX expression is highly correlated with lymphocyte extravasation at HEVs and that inhibition of ATX and LPA receptors resulted in strong impairment of lymphocyte trafficking into lymph nodes. LPA abrogated this suppression. These data strongly suggest that the ATX/ LPA axis is a positive regulator of lymphocyte extravasation at HEVs.

Research Products

• [Journal Article] Novel regulators of lymphocyte trafficking across high endothelial venules (2011)
  • Author(s): Umemoto, E., Hayasaka, H., Bai, Z., Cai, L., Yonekura, S., Peng, X., Takeda, A., Tohya, K. & Miyasaka, M.
  • Journal Title: Crit. Rev. Immunol.(Review) Volume: 312 Pages: 147-169
  • Peer Reviewed
• [Journal Article] Novel regulators of lymphocyte trafficking across high endothelial venules (2011)
  • Author(s): Umemoto, E., Hayasaka, H., Bai, Z., Cai, L., Yonekura, S., Peng, X., Takeda, A., Tohya, K., Miyasaka, M.
  • Journal Title: Crit.Rev.Immunol. Volume: 31(Review) Pages: 147-169
  • Peer Reviewed
• [Journal Article] Comparative analysis of the effects of anti-IL-6 receptor mAb and anti-TNF mAb treatment on CD4+ T cell responses in murine colitis. (2011)
  • Author(s): Terabe, F., Fujimoto, M., Serada, S., Shinzaki, S., Iijima, H., Tsujii, M., Hayashi, N., Nomura, S., Kawahata, H., Jang, M.H., Miyasaka, M., Mihara, M., Ohsugi, Y., Kishimoto, T., Naka, T
  • Journal Title: Inflamm.Bowel Dis. Volume: 17 Pages: 491-502
  • Peer Reviewed
• [Journal Article] Neogenesis and development of the high endothelial venules that mediate lymphocyte trafficking (2010)
  • Author(s): Hayasaka, H., Taniguchi, K., Fukai, S. & Miyasaka, M.
  • Journal Title: Cancer Sci.(Review) Volume: 101 Pages: 2302-2308
  • NAID: 10027833068
  • Peer Reviewed
• [Journal Article] Microanatomy of lymphocyte-endothelial interactions at the high endothelial venules of lymph nodes (2010)
  • Author(s): Tohya, K., Umemoto, E., & Miyasaka, M.
  • Journal Title: Histol. Histopathol.,(Review) Volume: 25 Pages: 781-794
  • Peer Reviewed
• [Journal Article] (equal contribution):: Rap1 controls lymphocyte adhesion cascade and interstitial migration within lymph nodes in RAPL-dependent and-independent manners (2010)
  • Author(s): *Ebisuno, Y., * Katagiri, K., Katakai, T., Ueda, Y., Nemoto, T., Inada, H., Nabekura, J., Okada, T., Kannagi, R., Tanaka, T., Miyasaka, M., Hogg, N. & Kinashi, T
  • Journal Title: Blood Volume: 115 Pages: 804-814
  • Peer Reviewed
• [Journal Article] Anti-arthritic activity of synthesized chondroitin sulfate Ehexasaccharide. (2010)
  • Author(s): Matsumoto, T., Inoue, T., Takahashi, A., Higuchi, A., Taniguchi-Morita, K., Miyasaka, M., Tamura, J.
  • Journal Title: Arzneimittelforschung Volume: 60 Pages: 754-759
  • Peer Reviewed
• [Journal Article] Neogenesis and development of the high endothelial venules that mediate lymphocyte trafficking. (2010)
  • Author(s): Hayasaka, H., Taniguchi, K., Fukai, S., Miyasaka, M.
  • Journal Title: Cancer Sci. Volume: 101 Pages: 2302-2308
  • NAID: 10027833068
  • Peer Reviewed
• [Journal Article] Two-state conformations in the hyaluronan-binding domain regulate CD44 adhesiveness under flow condition. (2010)
  • Author(s): Ogino, S., Nishida, N., Umemoto, R., Suzuki, M., Takeda, M., Terasawa, H., Kitayama, J., Matsumoto, M., Hayasaka, H., Miyasaka, M., Ichio, S.
  • Journal Title: Structure Volume: 18 Pages: 649-656
  • 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
  • Peer Reviewed
• [Journal Article] Microanatomy of lymphocyte-endothelial interactions at the high endothelial venules of lymph nodes. (2010)
  • Author(s): Tohya, K., Umemoto, E., Miyasaka, M.
  • Journal Title: Histol.Histopathol. Volume: 25 Pages: 781-794
  • 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: Canser Sci. Volume: 101 Pages: 363-368
  • NAID: 10026587701
  • Peer Reviewed
• [Journal Article] Rap1 controls lymphocyte adhesion cascades and interstitial migration within lymph nodes in a RAPL-dependent and independent manner. (2010)
  • Author(s): Ebisuno, Y., Katagiri, K., Katakai, T., Ueda, Y., Nemoto, T., Inada, H., Nabekura, J., Okada, T., Kannagi, R., Tanaka, T., Miyasaka, M., Hogg, N., Kinashi, T., (equal contribution)
  • Journal Title: Blood Volume: 115 Pages: 804-814
  • Peer Reviewed
• [Journal Article] Rap1 controls lymphocyte adhesion cascades and interstitial migration within lymph nodes in a RAPL-dependent and independent manner. (2010)
  • Author(s): *Ebisuno, Y., *Katagiri, K.(*equal contribution)
  • Journal Title: Blood 115 Pages: 804-814
  • 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.
  • Journal Title: Canser Sci. 101 Pages: 363-368
  • Peer Reviewed
• [Journal Article] (equal contribution): CXC chemokine ligand 12 promotes CCR7-dependent naive T-cell trafficking to lymph nodes and Peyer' s patches (2009)
  • Author(s): Bai, Z., * Hayasaka, H., Kobayashi, M., Li, W., Guo, Z., Jang, M. H., Kondo, A., Choi, B., Iwakura, Y. & Miyasaka, M
  • Journal Title: J. Immunol. Volume: 182 Pages: 1287-1295
  • Peer Reviewed
• [Journal Article] P-selectin glycoprotein ligand-1 negatively regulates T-cell immune resaonses. (2009)
  • Author(s): Matsumoto, M.
  • Journal Title: J.Immunol. 183 Pages: 7204-7211
  • Peer Reviewed
• [Journal Article] Constitutive expression of IDO by dendritic cells of mesenteric lymph nodes : functional involvement of the CTLA-4/B7 and CCL22/CCR4 interactions. (2009)
  • Author(s): Onodera, T.
  • Journal Title: J.Immunol. 183 Pages: 5608-5614
  • Peer Reviewed
• [Journal Article] CXCL 12 promotes CCR7-dependent nalve T-cell trafficking to lymph nodes and Peyer's patches. (2009)
  • Author(s): *Bai, Z., *Hayasaka, H(*equal contribution)
  • Journal Title: J.Immunol. 182 Pages: 1287-1295
  • Peer Reviewed
• [Journal Article] Microanatomy of lymphocyte-endothelial interactions at the high endothelial venules of lymph nodes.
  • Author(s): Tohya, K.
  • Journal Title: Histol. Histopathol. in press
  • Peer Reviewed
• [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, USA
• [Presentation] Inhibition of the Autotaxin/LPA axis results in inhibition of lymphocyte release from the endothelial cells of high endothelial venules in vitro (2011)
  • Author(s): Cai, L., Bai, Z., Umemoto, E., Hayasaka, H., Takeda, A., Miyasaka, M.
  • Organizer: The 40th annual meeting of the Japanese Society for Immunology
  • Place of Presentation: Chiba
  • Year and Date: 2011-11-29
• [Presentation] In vivo inhibition of the autotaxin/LPA axis results in inhibition of lymphocyte transmigration across high endothelial venules of lymph nodes (2011)
  • Author(s): Hata, E., Bai, Z., Cai, L., Umemoto, E., Hayasaka, H., Miyasaka, M.
  • Organizer: The 40th annual meeting of the Japanese Society for Immunology
  • Place of Presentation: Chiba
  • Year and Date: 2011-11-29
• [Presentation] Nepmucin/CD300LG promotes LPA-induced lymphocyte transcellular migration across HEV endothelial cells (2011)
  • Author(s): Takeda, A., Umemoto, E., Ikeno, T., Bai, Z., Miyasaka, M.
  • Organizer: The 40th annual meeting of the Japanese Society for Immunology
  • Place of Presentation: Chiba
  • Year and Date: 2011-11-29
• [Presentation] Autotaxin and Lysophosphatidic Acid Receptors : Potential Target Molecules in New Therapies for Rheumatoid Arthritis (2011)
  • Author(s): Miyabe, Y., Miyabe, C., Iwai, Y., Ebisawa, M., Miyasaka, M., Miyasaka, N., Nanki, T.
  • Organizer: The 40th annual meeting of the Japanese Society for Immunology
  • Place of Presentation: Chiba
  • Year and Date: 2011-11-28
• [Presentation] リンパ球の動態制御とリン脂質シグナリング (2011)
  • Author(s): 宮坂昌之
  • Organizer: 第8回健康発達医学研究会
  • Place of Presentation: 大阪(招待講演)
  • Year and Date: 2011-08-22
• [Presentation] Regulation of lymphocyte trafficking by lysophospholipids (2011)
  • Author(s): Miyasaka, M.
  • Organizer: Invited lecture. POSTECH IBB-Osaka Univ. IFReC exchange seminar
  • Place of Presentation: Korea
  • Year and Date: 2011-06-24
• [Presentation] Regulation of lymphocyte trafficking by lysophospholipids (2011)
  • Author(s): Miyasaka, M.
  • Organizer: POSTECH IBB-Osaka Univ.IFReC exchange seminar
  • Place of Presentation: Pohang, Korea(Invited lecture)
  • Year and Date: 2011-06-24
• [Presentation] Autotoxin, a new regulator of lymphocyte trafficking across high endothelial venules (2011)
  • Author(s): Miyasaka, M., Bai, Z., Cai, L., Hayasaka, H., Umemoto, E.
  • Organizer: JSICR-MMCB2011 joint meeting)
  • Place of Presentation: Osaka((Invited lecture)
  • Year and Date: 2011-05-25
• [Presentation] The autotaxin/lysophosphatidic acid axis regulates lymphocyte extravasation at lymph node high endothelial venules (2011)
  • 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, U.S.A.
  • Year and Date: 2011-01-09
• [Presentation] Inhibition of the Autotaxin/ LPA axis results in inhibition of lymphocyte release from the endothelial cells of high endothelial venules in vitro (2011)
  • Author(s): Cai, L., et al.
  • Organizer: The 40th annual meeting of the Japanese Society for Immunology
  • Place of Presentation: Chiba
• [Presentation] In vivo inhibition of the autotaxin/ LPA axis results in inhibition of lymphocyte transmigration across high endothelial venules of lymph nodes (2011)
  • Author(s): Hata, E., et al.
  • Organizer: The 40th annual meeting of the Japanese Society for Immunology
  • Place of Presentation: Chiba
• [Presentation] Nepmucin/ CD300LG promotes LPA-induced lymphocyte transcellular migration across HEV endothelial cells (2011)
  • Author(s): Takeda, A., et al.
  • Organizer: The 40th annual meeting of the Japanese Society for Immunology
  • Place of Presentation: Chiba
• [Presentation] HEV依存性リンパ球トラフィキングのautotaxinによる制御 (2011)
  • Author(s): 蔡林君、他
  • Organizer: 第35回日本リンパ学会総会
  • Place of Presentation: 東京
• [Presentation] リゾフォスファチジン酸を標的とした関節リウマチの新規治療法開発 (2011)
  • Author(s): 宮部斉重、他
  • Organizer: 第32回日本炎症・再生医学会
  • Place of Presentation: 京都
• [Presentation] Autotoxin, a new regulator of lymphocyte trafficking across high endothelial venules (2011)
  • Author(s): Miyasaka, M., et al.
  • Organizer: Invited lecture. JSICR-MMCB2011 joint meeting
  • Place of Presentation: Osaka
• [Presentation] The functional role of a lipid-generating enzyme, autotaxin, in lymphocyte trafficking across the venules of lymphoid tissues. (2010)
  • Author(s): Miyasaka, M., Bai, Z., Linjun Cai, L., Hayasaka, H., Umemoto, E.
  • Organizer: 2nd Synthetic Immunology Workshop
  • Place of Presentation: Kyoto(招待講演)
  • Year and Date: 2010-12-17
• [Presentation] How does a lipid mediator-generating enzyme, autotaxin, regulate lymphocyte trafficking across high endothelial venules? (2010)
  • Author(s): Miyasaka, M.
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: Kobe(招待講演)
  • Year and Date: 2010-08-24
• [Presentation] Luminal expression of autotaxin and its role in lymphocyte trafficking across the venules of lymphoid tissues. (2010)
  • Author(s): Bai, Z., Umemoto, E., Hayasaka, H., Cai, L., Aold, J., Okudaira, S., Jin, T., Ishii, M., Fujii, F., Watanabe, T., Miyasaka, M.
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: Kobe
  • Year and Date: 2010-08-24
• [Presentation] The role of an LPA-generating enzyme autotaxin in lymphocyte trafficking across the venules of lymphoid tissues. (2010)
  • Author(s): Cai, L., Bai, Z., Umemoto, E., Hayasaka, H., Miyasaka, M.
  • Organizer: The 31st Meeting of the Japanese Society of Inflammation and Regeneration
  • Place of Presentation: Tokyo
  • Year and Date: 2010-08-06
• [Presentation] The functional role of a lipid-generating enzyme, autotaxin, in lymphocyte trafficking across the venules of lymphoid tissues (2010)
  • Author(s): Miyasaka, M., et al.
  • Organizer: Invited lecture. 2nd Synthetic Immunology Workshop
  • Place of Presentation: Kyoto
• [Presentation] How does a lipid mediator-generating enzyme, autotaxin, regulate lymphocyte trafficking across high endothelial venules? Invited lecture (2010)
  • Author(s): Miyasaka, M.
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: Kobe
• [Presentation] Luminal expression of autotaxin and its role in lymphocyte trafficking across the venules of lymphoid tissues (2010)
  • Author(s): Bai, Z., et al.
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: Kobe
• [Presentation] The role of an LPA-generating enzyme autotaxin in lymphocyte trafficking across the venules of lymphoid tissues (2010)
  • Author(s): Cai, L., et al.
  • Organizer: The 31st Meeting of the Japanese Society of Inflammation and Regeneration
  • Place of Presentation: Tokyo
• [Presentation] How do immune cells cross the endothelial barrier? (2010)
  • Author(s): Miyasaka, M.
  • Organizer: ニュージーランド研究科学技術省ワークショップ
  • Place of Presentation: 大阪
• [Presentation] How do immune cells cross the endothelial barrier? Invited lecture (2009)
  • Author(s): Miyasaka, M., et al.
  • Organizer: The 39th Annual Meeting of the Japanese Society for Immunology
  • Place of Presentation: Osaka
• [Presentation] Luminal expression of autotaxin and its role in high endothelial venules (2009)
  • Author(s): Bai Z., et al.
  • Organizer: The 39th Annual Meeting of the Japanese Society for Immunology
  • Place of Presentation: Osaka
• [Presentation] Autotaxin, a new modulator of lymphocyte trafficking into lymph nodes (2009)
  • Author(s): Miyasaka, M., et al.
  • Organizer: 2nd European Congress of Immunology(ECI) 2009
  • Place of Presentation: Berlin, Germany
• [Presentation] リンパ球トラフィキングを制御する血管HEVの機能制御機構 (2009)
  • Author(s): 宮坂昌之
  • Organizer: 招待特別講演.第33回日本リンパ学会総会
  • Place of Presentation: 大阪
• [Presentation] How do immune cells cross the endothelial barrier?-Dogmas and Enigmas. Invited lecture (2009)
  • Author(s): Bai, Z., et al.
  • Organizer: Singapore-Osaka, 1st Joint SIgN-IFReC Meeting
  • Place of Presentation: Singapore
• [Presentation] CXCL12(SDF-1 alpha) Promotes CCR7-Dependent Naive T Cell Trafficking to Lymph Nodes and Peyer' s Patches (2009)
  • Author(s): Bai, Z., et al.
  • Organizer: The First International Kishimoto Foundation Symposium
  • Place of Presentation: Osaka
• [Presentation] リンパ球、樹状細胞の動態を決める分子機構 (2009)
  • Author(s): 宮坂昌之
  • Organizer: 招待講演.第36回佐島シンポジウム
  • Place of Presentation: 東京
• [Presentation] リンパ球、樹状細胞の動態を決める分子機構. (2009)
  • Author(s): 宮坂昌之
  • Organizer: 第36回佐島シンポジウム
  • Place of Presentation: 東京
• [Presentation] CXCL12(SDF-1α) Promotes CCR7-Dependent Naive T Cell Trafficking to Lvmph Nodes and Pever's Patches. (2009)
  • Author(s): Bai, Z.
  • Organizer: The First International Kishimoto Foundation Symposium
  • Place of Presentation: Osaka
• [Presentation] How do immune cells cross the endothelialbarrier?-Dogmas and Enigmas. (2009)
  • Author(s): Bai, Z.
  • Organizer: Singapore-Osaka, 1st Joint SlgN-IFReC Meeting
  • Place of Presentation: Singapore
• [Presentation] リンパ球トラフィキングを制御する血管HEVの機能制御機構. (2009)
  • Author(s): 宮坂昌之
  • Organizer: 第33回日本リンパ学会総会
  • Place of Presentation: 大阪
• [Presentation] Autotaxin, a new modulator of iymphocyte trafficking into lymph nodes. (2009)
  • Author(s): Miyasaka, M.
  • Organizer: 2nd European Congress of Immunology(ECI)2009
  • Place of Presentation: Berlin, Germany
• [Presentation] How do immune cells cross the endothelial barrier? (2009)
  • Author(s): Miyasaka, M.
  • Organizer: The 39th Annual Meeting of the Japanese Society for Immunology
  • Place of Presentation: Osaka
• [Presentation] Luminal expression of autotaxin and its role in high endothelial venules. (2009)
  • Author(s): Bai Z.
  • Organizer: The 39th Annual Meeting of the Japanese Society for Immunology
  • Place of Presentation: Osaka