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Contribution of vascular permeability for aging erythrocyte selection in spleen

Research Project

Project/Area Number 24659282
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Laboratory medicine
Research InstitutionKagoshima University

Principal Investigator

HASHIGUCHI Teruto  鹿児島大学, 医歯(薬)学総合研究科, 教授 (70250917)

Co-Investigator(Kenkyū-buntansha) ITO Takashi  鹿児島大学, 大学院医歯学総合研究科, 特任講師 (20381171)
OYAMA Yoko  鹿児島大学, 医学部・歯学部付属病院, 特任助教 (20583470)
SHIMIZU Toshiaki  鹿児島大学, 大学院医歯学総合研究科, 助教 (50468055)
Co-Investigator(Renkei-kenkyūsha) YAMAKUCHI Munekazu  鹿児島大学, 大学院医歯学総合研究科, 准教授 (20325814)
TAKENOUCHI Kazunori  鹿児島大学, 医学部・歯学部付属病院, 医員 (30646758)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords脾臓 / リンパ節 / 赤血球 / 血管透過性 / 血球貪食 / 免疫 / 鉄代謝 / VEGF-A / 貧血 / B細胞 / eryptosis / 病態検査学 / 血管内皮細胞増殖因子 / hepcidin / 鉄 / 脾 / 肝 / 血管新生 / 活性酸素 / 老化
Outline of Final Research Achievements

It has recently been reported that monocyte-derived dendritic cells perform “hemophagocytosis” to fine tune excessive immune responses. We generated CD19Cre/hVEGF-Afl mice that express human VEGF-A specifically in B-cells. We have shown that B-Cell derived VEGF-A promotes expansion of high endothelial venule (HEV) like structures within LNs accompanied by suppressing the ensuing immune responses. In this study we found that the active hemophagocytosis in LNs of CD19Cre/hVEGF-Afl mice were observed together with decreasing the number of CD8+ T cells and increasing PD-1 expression in CD8+ T cells. Also CD19Cre/hVEGF-Afl mice represented the phenotype corresponding with iron deficiency anemia. We concluded that B-cell derived VEGF-A executes tuning of immune response by decreasing the number of CD8+ T cells, increasing PD-1 expression in CD8+ T cells and hemophagocytosis. Our observations,“integrated immune system” will contribute to develop the new concept about B-cell biology.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (10 results)

All 2014 2013

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 2 results) Presentation (4 results)

  • [Journal Article] Upregulation of non-β Cell-derived Vascular Endothelial Growth FactorA Increases Small Clusters of Insulin producing Cells in the Pancreas.2014

    • Author(s)
      Takenouchi K, Shrestha B, Yamakuchi M, Yoshinaga M, Arimura N, Kawaguchi H, Nagasato T, Feil R, Kawahara K-I, Sakamoto T, Maruyama I, Hashiguchi T.
    • Journal Title

      Experimental and Clinical Endocrinology & Diabetes

      Volume: in press Issue: 05 Pages: 308-15

    • DOI

      10.1055/s-0034-1371811

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Toxic effects of extracellular histones and their neutralization by vitreous in retinal detachment.2014

    • Author(s)
      Kawano H, Ito T, Yamada S, Hashiguchi T, Maruyama I, Hisatomi T, Nakamura M, Sakamoto T.
    • Journal Title

      Laboratory Investigations

      Volume: 94(5) Issue: 5 Pages: 569-585

    • DOI

      10.1038/labinvest.2014.46

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Associations between the Autonomic Nervous System and the Second Derivative of the Finger Photoplethysmogram Indices2014

    • Author(s)
      Kohjitani A, Miyata M, Iwase Y, Ohno S, Tohya A, Manabe Y, Hashiguchi T, Sugiyama K.
    • Journal Title

      Journal of Atherosclerosis and Thrombosis

      Volume: 21 Issue: 5 Pages: 501-508

    • DOI

      10.5551/jat.19877

    • NAID

      130004444730

    • ISSN
      1340-3478, 1880-3873
    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Coffee polyphenols improve peripheral endothelial function after glucose loading in healthy male adults.2013

    • Author(s)
      Ochiai R, Sugiura Y, Shioya Y, Otsuka K, Katsuragi Y, Hashiguchi T.
    • Journal Title

      Nutrition Research

      Volume: 34 Issue: 2 Pages: 155-159

    • DOI

      10.1016/j.nutres.2013.11.001

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Recombinant thrombomodulin protects mice against histone-induced lethal thromboembolism.2013

    • Author(s)
      Nakahara M, Ito T, et al.
    • Journal Title

      PLoS One

      Volume: 8(9) Issue: 9 Pages: 75961-75961

    • DOI

      10.1371/journal.pone.0075961

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Saturated fatty acid palmitate induces extracellular release of histone H3 : a Possible mechanistic basis for high-fat diet-induced inflammation and thrombosis.2013

    • Author(s)
      Shrestha C, Ito T, et al.
    • Journal Title

      Biochemical and biophysical research communications

      Volume: 437(4) Issue: 4 Pages: 573-578

    • DOI

      10.1016/j.bbrc.2013.06.117

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Hemophagocytosis as a process of fine tuning immune system in vivo2014

    • Author(s)
      Shrestha Binita 伊藤隆史 郡山豊泰 竹之内和則 大山陽子 清水利昭 山口宗一 丸山征郎 橋口照人
    • Organizer
      第61回 日本臨床検査医学会学術集会
    • Place of Presentation
      福岡国際会議場(福岡県)
    • Year and Date
      2014-11-22 – 2014-11-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] Novel Insight of B Cell-Derived VEGF-A: Fine Tuning the Immune Response Through Hemophagocytosis2014

    • Author(s)
      Binita Shrestha, Takashi Ito, Naoki Miura, Kazunori Takenouchi, Sushil Panta, Munekazu Yamakuchi, Ikuro Maruyama, Teruto Hashiguchi
    • Organizer
      44th Annual Meeting of the German Society for Immunology
    • Place of Presentation
      BONN (Germany)
    • Year and Date
      2014-09-17 – 2014-09-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] マイクロRNAによる直腸がん細胞の低酸素応答制御2013

    • Author(s)
      山口宗一、清水利昭、竹之内和則、大山陽子、橋口照人
    • Organizer
      第60回 日本臨床検査医学会学術集会
    • Place of Presentation
      神戸
    • Related Report
      2013 Research-status Report
  • [Presentation] New Adipocytokine HMGB1 Inhibits Insulin Signaling in Adipocytes and Suppressed by Adiponection.2013

    • Author(s)
      Shimizu T, Yamakuchi M, Nakata M, Hashiguchi T, Maruyama I.
    • Organizer
      Merinoff World Congress 2013: HMGB1
    • Place of Presentation
      New York
    • Related Report
      2013 Research-status Report

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Published: 2013-05-31   Modified: 2021-12-22  

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