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

2013 Fiscal Year Final Research Report

• Project/Area Number: 24890149
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Digestive surgery
• Research Institution: The 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
• 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.

Research Products

• [Journal Article] Evidence for instant blood-mediated inflammatory reaction in clinical autologous islet transplantation (2014)
  • Author(s): Naziruddin B, Iwahashi S, Kanak MA, Takita M, Itoh T, Levy MF
  • Journal Title: Am J Transplant Volume: 14 Pages: 428-437
  • DOI: 10.1111/ajt.12558
  • Peer Reviewed
• [Journal Article] Laparoscopic hepatic resection for metastatic liver tumor of colorectal cancer : comparative analysis of short- and long-term results (2014)
  • Author(s): Iwahashi S, Shimada M, Utsunomiya T
  • Journal Title: Surg Endosc Volume: 28 Pages: 80-84
  • DOI: 10.1007/s00464-013-3165-3
  • Peer Reviewed
• [Journal Article] Cytokine expression in spleen affects progression of liver cirrhosis through liver-spleen cross-talk (2014)
  • 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)
  • Peer Reviewed
• [Journal Article] CXC receptor 4 and stromal cell-derived factor 1 in primary tumors and liver metastases of colorectal cancer (2014)
  • 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: J Surg Res Volume: 187 Pages: 107-112
  • DOI: 10.1016/j.jss.2013.10.030.
  • 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
  • DOI: 10.1111/hepr.12164.
  • Peer Reviewed
• [Journal Article] Changes of immunological parameters with administration of Japanese Kampo medicine (Juzen-Taihoto/TJ-48) in patients with advanced pancreatic cancer (2014)
  • 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 Pages: 81-86
  • DOI: 10.1007/s10147-013-0529-6
  • Peer Reviewed
• [Journal Article] Elevation of high-mobility group box 1 after clinical autologous islet transplantation and its inverse correlation with outcomes (2014)
  • 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 Pages: 153-165
  • DOI: 10.3727/096368912X658980.
  • Peer Reviewed
• [Journal Article] Regulatory T cells in the blood : a new marker of surgical stress (2013)
  • Author(s): Saito Y, Shimada M, Utsunomiya T, Morine Y, Imura S, Ikemoto T, Mori H, Hanaoka J, Iwahashi S, Yamada S, Asanoma M
  • Journal Title: Surg Today Volume: 43 Pages: 608-612
  • DOI: 10.1007/s00595-013-0517-5.
  • 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 Pages: 175-177
  • DOI: 10.1097/MPA.0b013e3182546e37.
  • Peer Reviewed
• [Journal Article] High expression of cancer stem cell markers in cholangiolocellular carcinoma (2013)
  • Author(s): Iwahashi S, Utsunomiya T, Shimada M
  • Journal Title: Surg Today Volume: 43(6) Pages: 654-660
  • DOI: 10.1007/s00595-012-0437-9.
  • Peer Reviewed
• [Journal Article] The protective effect of adipose-derived stem cells against liver injury by trophic molecules (2013)
  • Author(s): Saito Y, Shimada M, Utsunomiya T, Ikemoto T, Yamada S, Morine Y, Imura S, Mori H, Sugimoto K, Iwahashi S, Asanoma M
  • Journal Title: J Surg Res Volume: 180 Pages: 162-168
  • DOI: 10.1016/j.jss.2012.10.009.
  • Peer Reviewed
• [Journal Article] Outcome of hepatectomy in super-elderly patients with hepatocellular carcinoma (2012)
  • Author(s): Yamada S, Shimada M, Miyake H, Utsunomiya T, Morine Y, Imura S, Ikemoto T,Mori H, Hanaoka J, Iwahashi S, Saito Y
  • Journal Title: Hepatol Res Volume: 42 Pages: 454-458
  • DOI: 10.1111/j.1872-034X.2011.00952.x.
  • 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)
  • Year and Date: 20120920-22