A combination regimen of low-dose bortezomib and rapamycin prolonged the graft survival in a murine allogeneic islet transplantation model

So Hee Hong, Kihyun Kim, Jun Seop Shin, Hyunwoo Chung, Chung Gyu Park

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

As the first FDA-approved proteasome inhibitor drug, bortezomib has been used for the treatment of multiple myeloma and lymphoma. However, its effects alone or in combination with other immunosuppressants on allogeneic islet transplantation have not been reported so far. In this study, we showed that the short-term combination treatment of low-dose bortezomib and rapamycin significantly prolonged the survival of islet allografts. Short-term treatment of low-dose (0.05 mg/kg or 0.1 mg/kg) bortezomib reduced the MHC class II expression in dendritic cells (DCs) of alloantigen-sensitized mice, and prolonged the islet allograft survival for up to 50 days in diabetic mice. Notably, when bortezomib was combined with rapamycin, it induced islet-specific immunological tolerance which allowed the acceptance of a second graft without additional immunosuppression. This regimen dramatically reduced the alloantigen-specific IFN-γ-producing T cells in the spleen, and increased regulatory T cells both at the graft site and in the spleen. Therefore, we propose that short-term treatment of low-dose bortezomib and rapamycin could be a new tolerance-promoting immunosuppressive regimen for allogeneic islet transplantation.

Original languageEnglish
Pages (from-to)21-27
Number of pages7
JournalImmunology Letters
Volume216
DOIs
StatePublished - Dec 2019

Bibliographical note

Funding Information:
This study was supported by a grant from the Korea Healthcare Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (Project No. HI13C0954).

Funding Information:
This study was supported by a grant from the Korea Healthcare Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (Project No. HI13C0954).

Publisher Copyright:
© 2019

Keywords

  • Bortezomib
  • Islet transplantation
  • Rapamycin
  • Tolerance

Fingerprint

Dive into the research topics of 'A combination regimen of low-dose bortezomib and rapamycin prolonged the graft survival in a murine allogeneic islet transplantation model'. Together they form a unique fingerprint.

Cite this