Improving allogeneic islet transplantation by suppressing Th17 and enhancing Treg with histone deacetylase inhibitors

Koji Sugimoto, Takeshi Itoh, Morihito Takita, Masayuki Shimoda, Daisuke Chujo, Jeff A. Sorelle, Bashoo Naziruddin, Marlon F. Levy, Mitsuo Shimada, Shinichi Matsumoto

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Islet transplantation is a new treatment for achieving insulin independence for patients with severe diabetes. However, major drawbacks of this treatment are the long graft survival, the necessity for immunosuppressive drugs, and the efficacy of transplantation. Donor-specific transfusion (DST) has been shown to reduce rejection after organ transplantation, potentially through enhanced regulatory T-cell (Treg) activity. However, recent findings have shown that activated Treg can be converted into Th17 cells. 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.

Original languageEnglish (US)
Pages (from-to)408-415
Number of pages8
JournalTransplant International
Volume27
Issue number4
DOIs
StatePublished - 2014
Externally publishedYes

Keywords

  • T helper 17 cell
  • donor-specific transfusion
  • histone deacetylase inhibitor
  • islet transplantation
  • regulatory T cell

ASJC Scopus subject areas

  • Transplantation

Fingerprint

Dive into the research topics of 'Improving allogeneic islet transplantation by suppressing Th17 and enhancing Treg with histone deacetylase inhibitors'. Together they form a unique fingerprint.

Cite this