Effect of Cd40 Silenced Dendritic Cells by RNA Interference on Mice Skin Allograft Rejection

Karimi, Mohammad Hossein; Marzban, Saeed; Hajiyan, Mohammad Reza; Geramizadeh, Bita; Pourfathollah, Ali Akbar; Rajabiyan, Mohammad Hassan; Ebrahimnezhad, Salimeh

doi:10.2217/imt.14.112

Cited by 6 publications

(3 citation statements)

References 37 publications

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“…The skin allograft model is known to be the most potent and convenient experimental model for the study of immunologically mediated tissue rejection. To counteract rejection responses, various studies have examined its validity for the assessment of allograft rejection [ 1 , 2 , 3 , 4 , 5 , 6 ]. Our present study confirms that BoTA promotes skin allograft survival and reduces the occurrence of acute rejection.…”

Section: Discussionmentioning

confidence: 99%

Botulinum toxin A increases allograft tolerance in an experimental transplantation model: a preliminary study

et al. 2018

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BackgroundIdentifying novel and safe immunosuppressants is of crucial importance. Recently, there have been several studies revealing that botulinum toxin A significantly alleviates ischemia-reperfusion injuries.Emerging evidence shows that ischemia-reperfusion injuries contribute to innate immune activation, promoting rejection and inhibiting tolerance. Therefore, we hypothesized that a pretreatment with botulinum toxin A might decrease allograft rejection in a rat transplantation model. MethodsTwenty-four Lewis rats were randomly assigned to two groups consisting of 12 rats each, depending on whether skin allograft was performed after pretreatment with botulinum toxin A (BoTA group) or with normal saline (control group). The experimental group was pretreated with a subcutaneous injection of botulinum toxin A (10 IU), while the control group was pretreated with normal saline 5 days prior to surgery. The donor Brown-Norway rat dorsal skin was subsequently grafted to the recipient Lewis rats. The recipient wounds, measuring 2 cm × 2 cm, were made via dorsal skin excision through the panniculus carnosus. The donor skins of the same dimensions were obtained and transplanted onto the wounds and sutured with 4-0 nylon sutures. Mean graft survival time was measured in both groups. Quantitative reverse-transcriptase polymerase chain reaction and western blotting were performed to evaluate the gene/protein expression of CD4 and VEGF. ResultsThe mean graft survival time in the BoTA group was significantly longer than that of the control group (p=0.004). The relative mRNA and protein expression of CD4 was significantly lower in the BoTA group (p<0.001), while the relative mRNA and protein expression of VEGF was significantly higher in the BoTA group (p<0.001). ConclusionIn conclusion, our results show that botulinum toxin A prolongs the survival of skin allografts in a rat transplantation model.

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Section: Discussionmentioning

confidence: 99%

Botulinum toxin A increases allograft tolerance in an experimental transplantation model: a preliminary study

et al. 2018

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“…Tumor-derived exosomes (TEX) are modified by electroporation to overexpress miR-155, miR-142, and miR-let-7i, which can change the original immunosuppressive effect of TEX and induce DC maturation [ 15 ]. Compared with the untreated group, mice intravenously injected with DCs transduced with CD40 siRNA showed prolonged graft survival, increased Treg cells, fewer CD4+ and CD8+ T cells, and promoted T cell differentiation into Th2 cells [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of miR-let-7i Induces DC Immature Cells and Improves Skin Graft Tolerance

et al. 2022

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Dendritic cells (DC) initiate the immune response in the body. They can stimulate T cell activation, proliferation, and differentiation and ultimately participate in the immune response and the immune tolerance response. The purpose of this study was to coculture DCs and T cells and subcutaneously inject DCs transfected with miR-let-7i into rhesus monkey transplantations to verify the role of miR-let-7i in allograft immune tolerance. In vitro studies found that the expression of miR-let-7i was upregulated after inducing the maturation of DCs. The low expression of miR-let-7i inhibited the maturation of DCs, promoted the differentiation of T cells into T helper T cells 2 (Th2), and inhibited T helper T cell 1- (Th1-) driven rejection. In vivo studies also obtained similar results, and subcutaneous injection of DCs transfected with miR-let-7i inhibitor prolonged the survival time of allogeneic skin transplantation. Therefore, we conclude that inhibition of miR-let-7i inhibits DC maturation and improves the tolerance of grafted skin.

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“…Immune rejection is a well-known and inevitable issue in many immune response-related diseases, such as graft-versus-host disease, hypersensitivity, and autoimmune diseases. At present, conventional immunosuppressive (IS) drugs are commonly used to treat immune rejection, but they will incur many serious risks, including infection, malignancy, and drug toxicity [ 1 – 3 ]. Therefore, several researchers have focused on inducing immune tolerance in patients to address these intricate problems.…”

Section: Introductionmentioning

confidence: 99%

The Effect of Traditional Chinese Formula Danchaiheji on the Differentiation of Regulatory Dendritic Cells

Chen

Wang

et al. 2016

Evidence-Based Complementary and Alternative Medicine

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Recently, regulatory dendritic cells (DCregs), a newly described dendritic cell subset with potent immunomodulatory function, have attracted increased attention for their utility in treating immune response-related diseases, such as graft-versus-host disease, hypersensitivity, and autoimmune diseases. Danchaiheji (DCHJ) is a traditional Chinese formula that has been used for many years in the clinic. However, whether DCHJ can program dendritic cells towards a regulatory phenotype and the underlying mechanism behind this process remain unknown. Herein, we investigate the effects of traditional Chinese DCHJ on DCregs differentiation and a mouse model of skin transplantation. The current study demonstrates that DCHJ can induce dendritic cells to differentiate into DCregs, which are represented by high CD11b and low CD86 and HLA-DR expression as well as the secretion of IL-10 and TGF-β. In addition, DCHJ inhibited DC migration and T cell proliferation, which correlated with increased IDO expression. Furthermore, DCHJ significantly prolonged skin graft survival time in a mouse model of skin transplantation without any liver or kidney toxicity. The traditional Chinese formula DCHJ has the potential to be a potent immunosuppressive agent with high efficiency and nontoxicity.

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Effect of Cd40 Silenced Dendritic Cells by RNA Interference on Mice Skin Allograft Rejection

Abstract: Taken together, these data demonstrate that downregulation of CD40 in DCs can expand Treg cells and increase skin allograft survival.

Cited by 6 publications

References 37 publications

Botulinum toxin A increases allograft tolerance in an experimental transplantation model: a preliminary study

Botulinum toxin A increases allograft tolerance in an experimental transplantation model: a preliminary study

Inhibition of miR-let-7i Induces DC Immature Cells and Improves Skin Graft Tolerance

The Effect of Traditional Chinese Formula Danchaiheji on the Differentiation of Regulatory Dendritic Cells

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