樹状細胞におけるSema4Aの細胞内小胞輸送機構の解明

2016 Fiscal Year Research-status Report

• Project/Area Number: 15K08423
• Research Institution: Osaka University
• Principal Investigator: 野島 聡 大阪大学, 医学系研究科, 助教 (40528791)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 免疫学 / 好中球 / 血管炎

Outline of Annual Research Achievements

研究プロジェクトの本筋とは独立して、好中球に発現するSema4Dの重要性が見出されたため、これについて解析を行った。
ANCA関連血管炎の患者血清において、健常者に比して有意に可溶型Sema4Dが高値であることがELISAの結果から示された。また、フローサイトメトリーの結果から、ANCA関連血管炎の患者由来の好中球表面に発現する膜型Sema4Dが、健常者に比して有意に減少していることが示された。これらは、好中球上に発現する膜型Sema4Dが切断され可溶型になることが、ANCA関連血管炎の病態に重要な役割を持つことを示唆する結果と考えられた。
また、血管内皮細胞株とのin vitro共培養実験の結果から、血管内皮に発現するplexin B2が好中球上のSema4Dに作用することにより、好中球におけるneutrophil extracellular trap(NET)の放出を抑制するシグナルが伝達されることが分かった。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

好中球に発現するSema4Dの、ANCA関連血管炎の病態における重要性が見出された。また、Sema4D-plexin B2の機能の一部が解明された。

Strategy for Future Research Activity

Sema4Dの好中球機能、ANCA関連血管炎病態における重要性について、引き続き解析を行っていく。具体的には、NETの放出を制御するSema4D-plexin B2の機能について、より詳細に解析を行っていく。更に、抗Sema4D抗体またはリコンビナントplexin B2蛋白を用いた、in vivoおよびin vitro治療実験も進めていく。

Causes of Carryover

支給額と実際の必要経費の間にわずかな差額があったため。

Expenditure Plan for Carryover Budget

試薬・物品費等に充てる。

Research Products

• [Journal Article] Mutation in VPS33A affects metabolism of glycosaminoglycans: a new type of mucopolysaccharidosis with severe systemic symptoms. (2017)
  • 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.
  • Peer Reviewed / Open Access
• [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.
  • Peer Reviewed
• [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
• [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.
  • DOI: 10.1038/srep45504.
  • 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 JI, Nojima S, Tahara SI, Ohshima K, Okuzaki D, Morii E.
  • Journal Title: Lab Invest. Volume: 96 Pages: 517-525
  • DOI: 10.1038/labinvest.2016.28.
  • Peer Reviewed
• [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
  • DOI: 10.1038/srep25738.
  • Peer Reviewed / Open Access
• [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
  • 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.
  • Peer Reviewed
• [Journal Article] CKAP4 is a Dickkopf1 receptor and is involved in tumor progression. (2016)
  • Author(s): Kimura H, Fumoto K, Shojima K, Nojima S, Osugi Y, Tomihara H, Eguchi H, Shintani Y, Endo H, Inoue M, Doki Y, Okumura M, Morii E, Kikuchi A.
  • Journal Title: J Clin Invest. Volume: 126 Pages: 2689-2705.
  • DOI: 10.1172/JCI84658.
  • Peer Reviewed
• [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 JI, Morii E.
  • Journal Title: Cancer Sci. Volume: 107 Pages: 1345-1352.
  • DOI: 10.1111/cas.12999.
  • 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.
  • Peer Reviewed
• [Journal Article] Polarization of M2 macrophages requires Lamtor1 that integrates cytokine and amino-acid signals. (2016)
  • Author(s): Kimura T, Nada S, Takegahara N, Okuno T, Nojima S, Kang S, Ito D, 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.
  • DOI: 10.1038/ncomms13130.
  • Peer Reviewed / Open Access
• [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.
  • Peer Reviewed