Sirtinol regulates the balance of Th17/Treg to prevent allograft rejection

Current immunosuppressive medications used after transplantation induce significant toxicity , and a new medication regimen is needed. Based on recent research, Sirt1 exerts a proinflammatory effect on the immune response. Sirtinol is a Sirt1 inhibitor, but its impact on allograft rejection and its...

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Bibliographic Details
Published in:Cell & bioscience 2017-10, Vol.7 (1), p.55-55, Article 55
Main Authors: Ye, Qing, Zhang, Mingjian, Wang, Yang, Fu, Shangxi, Han, Shu, Wang, Liming, Wang, Quanxing
Format: Article
Language:English
Subjects:
Allograft rejection
Allografts
CD4 antigen
Cell cycle
Cellular proteins
Cytomegalovirus
Epigenetics
Foxp3 protein
Graft rejection
Heart
Heart transplantation
Helper cells
Immunosuppressive agents
Inflammation
Lymphocytes
Lymphocytes T
Molecular modelling
Prevention
Prostate cancer
Senescence
SIRT1 protein
Sirtinol
Splenocytes
Studies
T cells
Tacrolimus
Th17/Treg
Toxicity
Transplants & implants
Tumor necrosis factor-TNF
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Summary:Current immunosuppressive medications used after transplantation induce significant toxicity , and a new medication regimen is needed. Based on recent research, Sirt1 exerts a proinflammatory effect on the immune response. Sirtinol is a Sirt1 inhibitor, but its impact on allograft rejection and its molecular mechanisms of action have not yet been reported. In this study, we examined the effect of sirtinol on prolonging allograft survival in a mouse cervical heterotopic heart transplantation model. Based on an examination of the allograft, allografts from sirtinol-treated recipients show significantly lower levels of IL-17A expression and higher levels of Foxp3 expression. In vivo, sirtinol reduces the proportion of Th17 cells and increases the proportion of Treg cells in splenocytes from recipients. In vitro, sirtinol reduces the proportion of Th17 cells and decreases the expression of IL-17A and RORγt in an isolated CD4 T cell population. Moreover, we identified synergistic effects of sirtinol and FK506 on prolonging allograft survival, and sirtinol synergizes with FK506 to promote Foxp3 expression. Sirtinol, a Sirt1 inhibitor, may be a promising immunosuppressive drug to prevent the rejection reaction in combination with FK506.
ISSN:2045-3701
2045-3701
DOI:10.1186/s13578-017-0182-2