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The induction of immune tolerance and the improvement islet transplantation with histone deacetylase inhibitors.

Research Project

Project/Area Number 24890149
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Digestive surgery
Research InstitutionThe University of Tokushima

Principal Investigator

IWAHASHI Shuichi  徳島大学, 大学病院, 特任助教 (30531751)

Project Period (FY) 2012-08-31 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords免疫寛容誘導 / ドナー特異的輸血 / ヒストン脱アセチル化酵素阻害剤
Research Abstract

We focused on histone deacetylase inhibitors (HDACi) because it was reported that inhibition of HDAC activity prevented Treg differentiation into IL17-producing cells. We therefore sought to enhance Treg while suppressing Th17 cells using DST with HDACi to prolong graft survival. To stimulate Treg by DST, we used donor splenocytes. In DST with HDACi group, Foxp3 mRNA expression and Treg population increased in the thymus and spleen, whereas Th17 population decreased. qPCR analysis of lymphocyte mRNA indicated that Foxp3, IL-10, and TGF-b expression increased. However, interleukin 17a, Stat3 (Th17), and IFN-g expression decreased in DST + HDACi group, relative to DST alone. Moreover, DST treated with HDACi prolonged graft survival relative to controls in mice islet transplantation. DST with HDACi may therefore have utility in islet transplantation.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • Research Products

    (14 results)

All 2014 2013 2012

All Journal Article (13 results) (of which Peer Reviewed: 13 results) Presentation (1 results)

  • [Journal Article] Evidence for instant blood-mediated inflammatory reaction in clinical autologous islet transplantation2014

    • Author(s)
      Naziruddin B, Iwahashi S, Kanak MA, Takita M, Itoh T, Levy MF
    • Journal Title

      Am J Transplant

      Volume: 14 Issue: 2 Pages: 428-437

    • DOI

      10.1111/ajt.12558

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cytokine expression in spleen affects progression of liver cirrhosis through liver-spleen cross-talk2014

    • Author(s)
      Asanoma M, Ikemoto T, Mori H, Utsunomiya T, Imura S, Morine Y, Iwahashi S, Saito Y, Yamada S, Shimada M
    • Journal Title

      Hepatol Res

      Volume: (in press)

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Specific miRNA expression profiles of non-tumor liver tissue predict a risk for recurrence of hepatocellular carcinoma.2014

    • Author(s)
      Utsunomiya T, Ishikawa D, Asanoma M, Yamada S, Iwahashi S, Kanamoto M, Arakawa Y, Ikemoto T, Morine Y, Imura S, Ishibashi H, Takasu C, Shimada M.
    • Journal Title

      Hepatol Res.

      Volume: 印刷中 Issue: 6 Pages: 631-638

    • DOI

      10.1111/hepr.12164

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Elevation of high-mobility group box 1 after clinical autologous islet transplantation and its inverse correlation with outcomes2014

    • Author(s)
      Itoh T, Iwahashi S, Kanak MA, Shimoda M, Takita M, Chujo D, Tamura Y, Rahman AM, Chung WY, Onaca N, Coates PT, Dennison AR, Naziruddin B, Levy MF, Matsumoto S
    • Journal Title

      Cell Transplant

      Volume: 23 Issue: 2 Pages: 153-165

    • DOI

      10.3727/096368912x658980

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Improving allogeneic islet transplantation by suppressing Th17 and enhancing Treg with histone deacetylase inhibitors2014

    • Author(s)
      Sugimoto K, Itoh T, Takita M, Shimoda M, Chujo D, SoRelle JA, Naziruddin B, Levy MF, Shimada M, Matsumoto S
    • Journal Title

      Transpl Int

      Volume: 27(4) Issue: 4 Pages: 408-415

    • DOI

      10.1111/tri.12265

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Laparoscopic hepatic resection for metastatic liver tumor of colorectal cancer: comparative analysis of short- and long-term results.2013

    • Author(s)
      Iwahashi S , Shimada M, Utsunomiya T, Imura S, Morine Y, Ikemoto T, Arakawa Y, Mori H, Kanamoto M, Yamada S.
    • Journal Title

      Surgical Endoscopy

      Volume: 28 Issue: 1 Pages: 80-84

    • DOI

      10.1007/s00464-013-3165-3

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] CXC receptor 4 and stromal cell-derived factor 1 in primary tumors and liver metastases of colorectal cancer.2013

    • Author(s)
      Yamada S, Shimada M, Utsunomiya T, Morine Y, Imura S, Ikemoto T, Mori H, Arakawa Y, Kanamoto M, Iwahashi S, Saito Y.
    • Journal Title

      Journal of Surgical Research

      Volume: 187 Issue: 1 Pages: 107-112

    • DOI

      10.1016/j.jss.2013.10.030

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Changes of immunological parameters with administration of Japanese Kampo medicine (Juzen-Taihoto/TJ-48) in patients with advanced pancreatic cancer.2013

    • Author(s)
      Ikemoto T, Shimada M, Iwahashi S, Saito Y, Kanamoto M, Mori H, Morine Y, Imura S, Utsunomiya T.
    • Journal Title

      Int J Clin Oncol.

      Volume: 19 Issue: 1 Pages: 81-86

    • DOI

      10.1007/s10147-013-0529-6

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulatory T cells in the blood: a new marker of surgical stress.2013

    • Author(s)
      Yu Saito
    • Journal Title

      Surgery Today

      Volume: 43 Issue: 6 Pages: 608-612

    • DOI

      10.1007/s00595-013-0517-5

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Autoimmune chronic pancreatitis with IgG4-related pancreatic pseudocyst in a patient undergoing total pancreatectomy followed by autologous islet transplantation: a case report.2013

    • Author(s)
      Takita M, Itoh T, Matsumoto S, Shimoda M, Chujo D, Iwahashi S, Tamura Y, Onaca N, Naziruddin B, Bartlett BL, Levy MF
    • Journal Title

      Pancreas

      Volume: 42 Issue: 1 Pages: 175-177

    • DOI

      10.1097/mpa.0b013e3182546e37

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] High expression of cancer stem cell markers in cholangiolocellular carcinoma2013

    • Author(s)
      Iwahashi S, Utsunomiya T, Shimada M
    • Journal Title

      Surg Today

      Volume: 43(6) Issue: 6 Pages: 654-660

    • DOI

      10.1007/s00595-012-0437-9

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The protective effect of adipose-derived stem cells against liver injury by trophic molecules.2013

    • Author(s)
      Yu Saito
    • Journal Title

      Journal of Surgical Research

      Volume: 180 Issue: 1 Pages: 162-168

    • DOI

      10.1016/j.jss.2012.10.009

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Outcome of hepatectomy in super-elderly patients with hepatocellular carcinoma2012

    • Author(s)
      Yamada S, Shimada M, Utsunomiya T, et al.
    • Journal Title

      Hepatol res

      Volume: (in press) Issue: 5 Pages: 454-458

    • DOI

      10.1111/j.1872-034x.2011.00952.x

    • NAID

      10031144259

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Presentation] Naziruddin B, Levy M.F.自家膵島移植におけるInstant blood-mediated inflammatory reaction発現の検討2012

    • Author(s)
      岩橋衆一,島田光生,宇都宮徹,森根裕二,居村暁,池本哲也,松本慎一
    • Organizer
      第48回日本移植学会総会
    • Place of Presentation
      愛知県(愛知県労働産業センター)
    • Related Report
      2013 Final Research Report

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Published: 2012-11-27   Modified: 2019-07-29  

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