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Intracellular function of Sema4A in dendritic cells.

Research Project

Project/Area Number 15K08423
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Experimental pathology
Research InstitutionOsaka University

Principal Investigator

Nojima Satoshi  大阪大学, 医学系研究科, 助教 (40528791)

Co-Investigator(Renkei-kenkyūsha) KUMANOGOH Atsushi  大阪大学, 大学院医学系研究科, 教授 (10294125)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords自己免疫性疾患 / ANCA関連血管炎 / 免疫セマフォリン / 免疫学 / 好中球 / 血管炎 / 樹状細胞 / エクソソーム
Outline of Final Research Achievements

Since an interesting association between SEMA4D and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) was found, we studied the significance of SEMA4D in the pathogenesis of AAV. Serum levels of soluble SEMA4D were elevated in patients with AAV and correlated with disease activity scores. Cell-surface expression of SEMA4D was downregulated in neutrophils from patients with AAV, a consequence of proteolytic cleavage of membrane SEMA4D. Membranous SEMA4D on neutrophils bound to plexin B2 on endothelial cells, and this interaction decreased NET formation. Recombinant plexin B2 successfully inhibited pathogen-induced or ANCA-induced oxidative burst and NET formation.
Thus, neutrophil surface SEMA4D functions as a negative regulator of neutrophil activation. Proteolytic cleavage of SEMA4D as observed in patients with AAV may amplify neutrophil-mediated inflammatory responses. SEMA4D is a promising biomarker and potential therapeutic target for AAV.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report

Research Products

(25 results)

All 2018 2017 2016 2015

All Journal Article (25 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 24 results,  Open Access: 18 results,  Acknowledgement Compliant: 12 results)

  • [Journal Article] Anti-glypican-1 antibody-drug conjugate exhibits potent preclinical antitumor activity against glypican-1 positive uterine cervical cancer2018

    • Author(s)
      Matsuzaki S, Serada S, Hiramatsu K, Nojima S, Matsuzaki S, Ueda Y, Ohkawara T, Mabuchi S, Fujimoto M, Morii E, Yoshino K, Kimura T, Naka T.
    • Journal Title

      Int J Cancer

      Volume: 142 Pages: 1056-1066

    • DOI

      10.1002/ijc.31124

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] LSR Antibody Therapy Inhibits Ovarian Epithelial Tumor Growth by Inhibiting Lipid Uptake2018

    • Author(s)
      Hiramatsu K, Serada S, Enomoto T, Takahashi Y, Nakagawa S, Nojima S, Morimoto A, Matsuzaki S, Yokoyama T, Takahashi T, Fujimoto M, Takemori H, Ueda Y, Yoshino K, Morii E, Kimura T, Naka T
    • Journal Title

      Cancer Res.

      Volume: 78 Pages: 516-27

    • DOI

      10.1158/0008-5472.can-17-0910

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Adenylosuccinate lyase enhances aggressiveness of endometrial cancer by increasing killer cell lectin-like receptor C3 expression by fumarate2018

    • Author(s)
      Park Haengki、Ohshima Kenji、Nojima Satoshi、Tahara Shinichiro、Kurashige Masako、Hori Yumiko、Okuzaki Daisuke、Wada Naoki、Ikeda Jun-ichiro、Morii Eiichi
    • Journal Title

      Lab Invest.

      Volume: in press Pages: 449-461

    • DOI

      10.1038/s41374-017-0017-0

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Semaphorin 4D inhibits neutrophil activation and is involved in the pathogenesis of neutrophil-mediated autoimmune vasculitis2017

    • Author(s)
      Nishide M, Nojima S, Ito D, Takamatsu H, Koyama S, Kang S, Kimura T, Morimoto K, Hosokawa T, Hayama Y, Kinehara Y, Kato Y, Nakatani T, Nakanishi Y, Tsuda T, Park JH, Hirano T, Shima Y, Narazaki M, Morii E, Kumanogoh A.
    • Journal Title

      Ann Rheum Dis.

      Volume: 76 Pages: 1440-1448

    • DOI

      10.1136/annrheumdis-2016-210706

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Glypican-1 targeted antibody-based therapy induces preclinical antitumor activity against esophageal squamous cell carcinoma2017

    • Author(s)
      Harada E, Serada S, Fujimoto M, Takahashi Y, Takahashi T, Hara H, Nakatsuka R, Sugase T, Nishigaki T, Saito Y, Hiramatsu K, Nojima S, Mitsuo R, Ohkawara T, Morii E, Mori M, Doki Y, Kaneda Y, Naka T.
    • Journal Title

      Oncotarget

      Volume: 8 Pages: 24741-24752

    • DOI

      10.18632/oncotarget.15799

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lamtor1 Is Critically Required for CD4+ T Cell Proliferation and Regulatory T Cell Suppressive Function.2017

    • Author(s)
      Hosokawa T, Kimura T, Nada S, Okuno T, Ito D, Kang S, Nojima S, Yamashita K, Nakatani T, Hayama Y, Kato Y, Kinehara Y, Nishide M, Mikami N, Koyama S, Takamatsu H, Okuzaki D, Ohkura N, Sakaguchi S, Okada M, Kumanogoh A.
    • Journal Title

      J Immunol

      Volume: 199 Pages: 2008-2019

    • DOI

      10.4049/jimmunol.1700157

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CUBIC pathology: three-dimensional imaging for pathological diagnosis2017

    • Author(s)
      Nojima Satoshi、Susaki Etsuo A.、Yoshida Kyotaro、Takemoto Hiroyoshi、Tsujimura Naoto、Iijima Shohei、Takachi Ko、Nakahara Yujiro、Tahara Shinichiro、Ohshima Kenji、Kurashige Masako、Hori Yumiko、Wada Naoki、Ikeda Jun-ichiro、Kumanogoh Atsushi、Morii Eiichi、Ueda Hiroki R.
    • Journal Title

      Sci Rep.

      Volume: 7 Pages: 9269-9269

    • DOI

      10.1038/s41598-017-09117-0

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Peripheral blood monocyte count reflecting tumor-infiltrating macrophages is a predictive factor of adverse pathology in radical prostatectomy specimens2017

    • Author(s)
      Hayashi T, Fujita K, Nojima S, Hayashi Y, Nakano K, Ishizuya Y, Wang C, Yamamoto Y, Kinouchi T, Matsuzaki K, Kawamura N, Jingushi K, Kawashima A, Nagahara A, Ujike T, Uemura M, Imamura R, Morii E, Nonomura N.
    • Journal Title

      Prostate.

      Volume: 77 Pages: 1383-1388

    • DOI

      10.1002/pros.23398

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mutation in VPS33A affects metabolism of glycosaminoglycans: a new type of mucopolysaccharidosis with severe systemic symptoms2017

    • Author(s)
      Kondo H, Maksimova N, Otomo T*,Kato H, Imai A, Asano Y, Kobayashi K, Nojima S, Nakaya A, Hamada Y, Irahara K, Gurinova E, Sukhomyasova A, Nogovicina A, Savvina M, Yoshimori T, Ozono K Sakai N*
    • Journal Title

      Hum Mol Genet.

      Volume: 26 Pages: 173-183

    • DOI

      10.1093/hmg/ddw377

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Immunohistochemical analysis of the novel marginal-zone B-cell marker IRTA1 in malignant lymphoma.2017

    • Author(s)
      Ikeda JI, Kohara M, Tsuruta Y, Nojima S, Tahara S, Ohshima K, Kurashige M, Wada N, Morii E.
    • Journal Title

      Hum Pathol.

      Volume: 59 Pages: 70-79

    • DOI

      10.1016/j.humpath.2016.09.011

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Characterizing Semaphorin-Mediated Immune Responses Using an Antigen-Presentation Assay.2017

    • Author(s)
      Nojima S, Kumanogoh A.
    • Journal Title

      Methods Mol Biol.

      Volume: 1493 Pages: 379-391

    • DOI

      10.1007/978-1-4939-6448-2_27

    • Related Report
      2016 Research-status Report
  • [Journal Article] Argininosuccinate Synthase 1-Deficiency Enhances the Cell Sensitivity to Arginine through Decreased DEPTOR Expression in Endometrial Cancer.2017

    • Author(s)
      Ohshima K, Nojima S, Tahara S, Kurashige M, Hori Y, Hagiwara K, Okuzaki D, Oki S, Wada N, Ikeda JI, Kanai Y, Morii E.
    • Journal Title

      Sci Rep.

      Volume: 7 Pages: 45504-45504

    • DOI

      10.1038/srep45504

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Requirement of CXCL12-CXCR7 signaling for CD20- CD138- double-negative population in lymphoplasmacytic lymphoma.2016

    • Author(s)
      Wada N, Ikeda J, Nojima S, Tahara S, Ohshima K, Okuzaki D, Morii E.
    • Journal Title

      Lab Invest

      Volume: 96 Pages: 517-25

    • DOI

      10.1038/labinvest.2016.28

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] LRRK1 is critical in the regulation of B-cell responses and CARMA1-dependent NF-κB activation.2016

    • Author(s)
      Morimoto K, Baba Y, Shinohara H, Kang S, Nojima S, Kimura T, Ito D, Yoshida Y, Maeda Y, Sarashina-Kida H, Nishide M, Hosokawa T, Kato Y, Hayama Y, Kinehara Y, Okuno T, Takamatsu H, Hirano T, Shima Y, Narazaki M, Kurosaki T, Toyofuku T, Kumanogoh A.
    • Journal Title

      Sci. Rep.

      Volume: 6 Pages: 25738-25738

    • DOI

      10.1038/srep25738

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Prognostic significance of a component of the Hippo pathway, TAZ, in human uterine endometrioid adenocarcinoma.2016

    • Author(s)
      Zhan M, Ikeda JI, Wada N, Hori Y, Nojima S, Tahara SI, Ueda Y, Yoshino K, Kimura T, Morii E.
    • Journal Title

      Oncol Lett.

      Volume: 11 Pages: 3611-3616

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Overexpression of glypican-1 implicates poor prognosis and their chemoresistance in oesophageal squamous cell carcinoma.2016

    • Author(s)
      Hara, H., Takahashi, T., Serada, S., Fujimoto, M., Ohkawara, T., Nakatsuka, R., Harada, E., Nishigaki, T., Takahashi, Y., Nojima, S., Miyazaki, Y., Makino, T., Kurokawa, Y., Yamasaki, M., Miyata, H., Nakajima, K., Takiguchi, S., Morii, E., Mori, M., Doki, Y., Naka, T.
    • Journal Title

      Br J Cancer.

      Volume: 115 Pages: 66-75

    • DOI

      10.1038/bjc.2016.183

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] CKAP4 is a Dickkopf1 receptor and is involved in tumor progression2016

    • Author(s)
      Kimura, H., Fumoto, K., Shojima, K., Nojima, S., Osugi, Y., Tomihara, H., Eguchi, H., Shintani, Y., Endo, E., Inoue, M., Doki, Y., Okumura, M., Morii, E., and Kikuchi, A.
    • Journal Title

      J Clin Invest.

      Volume: 126 Pages: 2689-2705

    • DOI

      10.1172/jci84658

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] S100A4 accelerates the proliferation and invasion of endometrioid carcinoma and is associated with the ‘MELF’ pattern.2016

    • Author(s)
      Tahara S, Nojima S, Ohshima K, Hori Y, Kurashige M, Wada N, Ikeda J, Morii E.
    • Journal Title

      Cancer Sci.

      Volume: 109 Pages: 1345-1352

    • DOI

      10.1111/cas.12999

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Decreased fucosylated PSA as a urinary marker for high Gleason score prostate cancer.2016

    • Author(s)
      Fujita K, Hayashi T, Matsuzaki K, Nakata W, Masuda M, Kawashima A, Ujike T, Nagahara A, Tsuchiya M, Kobayashi Y, Nojima S, Uemura M, Morii E, Miyoshi E, Nonomura N.
    • Journal Title

      Oncotarget.

      Volume: 7 Pages: 56643-56649

    • DOI

      10.18632/oncotarget.10987

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Polarization of M2 macrophages requires Lamtor1 that integrates cytokine and amino-acid signals2016

    • Author(s)
      Kimura T, Nada S, Takegahara N, OkunoT, NojimaS, Kang S, Ito D, Morimoto K, Morimoto K, Hosokawa T, Hayama Y, Mitsui Y, Sakurai N, Sarashina-Kida H, Nishide M, Maeda Y, Takamatsu H, Okuzaki D, Yamada M, Okada M, Kumanogoh A.
    • Journal Title

      Nat Commun

      Volume: 7 Pages: 13130-13130

    • DOI

      10.1038/ncomms13130

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] ID1 upregulation and FoxO3a downregulation by Epstein-Barr virus-encoded LMP1 in Hodgkin's lymphoma.2016

    • Author(s)
      Ikeda JI, Wada N, Nojima S, Tahara S, Tsuruta Y, Oya K, Morii E.
    • Journal Title

      Mol Clin Oncol.

      Volume: 5 Pages: 562-566

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] 1.Semaphorin 4D contributes to rheumatoid arthritis by inducing inflammatory cytokine production: Pathogenic and therapeutic implications2015

    • Author(s)
      Yoshida Y, Ogata A, Kang S, Ebina K, Shi K, Nojima S, Kimura T, Ito D, Morimoto K, Nishide M, Hosokawa T, Hirano T, Shima Y, Narazaki M, Tsuboi H, Saeki Y, Tomita T, Tanaka T, Kumanogoh A.
    • Journal Title

      Arthritis Rheumatol.

      Volume: none Pages: 1481-1490

    • DOI

      10.1002/art.39086

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The Wnt5a-Ror2 axis promotes the signaling circuit between interleukin-12 and interferon-γ in colitis.2015

    • Author(s)
      Sato, A., Kayama, H., Shojima, K., Matsumoto, S., Koyama, H., Minami, Y., Nojima, S., Morii, E., Honda, H., Takeda, K., Kikuchi, A.
    • Journal Title

      Scientific Rep.

      Volume: 5 Pages: 10536-10536

    • DOI

      10.1038/srep10536

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] mTOR Complex Signaling through the SEMA4A-Plexin B2 Axis Is Required for Optimal Activation and Differentiation of CD8+ T Cells.2015

    • Author(s)
      Ito D, Nojima S*, Nishide M, Okuno T, Takamatsu H, Kang S, Kimura T, Yoshida Y, Morimoto K, Maeda Y, Hosokawa T, Toyofuku T, Ohshima J, Kamimura D, Yamamoto M, Murakami M, Morii E, Rakugi H, Isaka Y, Kumanogoh A*. (* correspondence)
    • Journal Title

      J Immunol

      Volume: 195 Pages: 934-43

    • DOI

      10.4049/jimmunol.1403038

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Anti-Cancer Effects of Nonequilibrium Atmospheric Pressure Plasma on Cancer-Initiating Cells in Human Endometrioid Adenocarcinoma Cells.2015

    • Author(s)
      Ikeda J, Tsuruta Y, Nojima S, Sakakita H, Hori M, Ikehara Y.
    • Journal Title

      Plasma Processes and Polymers.

      Volume: 12 Pages: 1370-1376

    • DOI

      10.1002/ppap.201500097

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant

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Published: 2015-04-16   Modified: 2019-03-29  

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