IL-17 Deficiency Attenuates Allograft Injury and Prolongs Survival in a Murine Model of Fully MHC-Mismatched Renal Allograft Transplantation

Kwan, Tak; Chadban, Steven J.; Ma, Jin; Bao, Shisan; Alexander, Stephen I.; Wu, Huiling

doi:10.1111/ajt.13140

Cited by 34 publications

(26 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Studies have shown that CD4 + CD25+ T cells play a key role in immune tolerance models [22,23]. Recent studies found IL-17 levels were increased in acute rejection of animal models or patients after early transplantation of the kidneys, lungs and heart [24][25][26]. In our study, the elevated expression of IL-17 was observed in an acute rejection model of SFS liver transplantation in rats.…”

Section: Discussionsupporting

confidence: 64%

RETRACTED ARTICLE: Approaching treatment for immunological rejection of living-donor liver transplantation in rats

et al. 2020

View full text Add to dashboard Cite

Background: The anti-immunological rejection therapy for small-for-size syndrome (SFSS) after live donor liver transplantation (LDLT) play a central role in keeping graft survival. The hepatocyte number and grafts function has undergone real-time changes with the proliferation and apoptosis of the grafts after reperfusion. Lacking an accurate and effective treatment regiments or indicators to guide the use of immunosuppressive drugs in SFS liver transplantation has made immunotherapy after SFS liver transplantation an urgent problem to be solved. Herein, we established small-for-size (SFS) and normal size liver transplantation model in rats to explore the effective indicators in guiding immunotherapy, to find an effective way for overcoming SFSS.Methods: Lewis rats (donors) and BN rats (recipients) were used to mimic allograft liver transplantation and treated with tacrolimus. Local graft immune response was analyzed through haematoxylin and eosin and immunohistochemistry. Flow cytometry was used to assess the overall immune status of recipient. The pharmacokinetics mechanism of immunosuppressive drugs was explored through detecting CYP3A2 expression at mRNA level and protein levels. Results:The results showed the local immune reaction of SFS grafts and systemic immune responses of recipient were significantly increased compared with those in normal size grafts and their recipient at four days after liver transplantation. Regression equation was used to regulate the tacrolimus dose which not only controlled tacrolimus serum concentration effectively but alleviated liver damage and improved survival rate.Conclusions: This study showed that AST level and tacrolimus serum concentrations are effective indicators in guiding immunotherapy. Regression equation (T D = − 0.494T C -0.0035AST + 260.487) based on AST and tacrolimus serum concentration can be used as a reference for adjustment of immunotherapy after SFS liver transplantation, which is applicable in clinical practice.

show abstract

Section: Discussionsupporting

confidence: 64%

RETRACTED ARTICLE: Approaching treatment for immunological rejection of living-donor liver transplantation in rats

et al. 2020

View full text Add to dashboard Cite

show abstract

“…The Th17 pathway has been implicated in acute T cell–mediated renal allograft rejection . We therefore evaluated IL‐17 expression by donor‐reactive T cells pre‐ and 4 weeks posttransplant (Figure A).…”

Section: Resultsmentioning

confidence: 99%

Renal Allograft Survival in Nonhuman Primates Infused With Donor Antigen-Pulsed Autologous Regulatory Dendritic Cells

Ezzelarab

Raïch‐Regué

Лу

et al. 2017

American Journal of Transplantation

View full text Add to dashboard Cite

Systemic administration of autologous regulatory dendritic cells (DCreg; unpulsed or pulsed with donor antigen [Ag]), prolongs allograft survival and promotes transplant tolerance in rodents. Here, we demonstrate that nonhuman primate (NHP) monocyte-derived DCreg pre-loaded with cell membrane vesicles from allogeneic PBMC, induce T cell hyporesponsiveness to donor alloAg in vitro. These donor alloAg-pulsed autologous DCreg (1.4–3.6 x 106/kg) were administered intravenously, one day before MHC-mismatched renal transplantation to rhesus monkeys treated with costimulation blockade (cytotoxic T lymphocyte Ag 4 [CTLA4] Ig) and tapered rapamycin. Prolongation of graft median survival time from 39.5 days (no DCreg infusion; n=6 historical controls) and 29 days with control unpulsed DCreg (n=2), to 56 days with donor Ag-pulsed DCreg (n=5), was associated with evidence of modulated host CD4+ and CD8+ T cell responses to donor Ag and attenuation of systemic IL-17 production. Circulating anti-donor antibody (Ab) was not detected until CTLA4Ig withdrawal. One monkey treated with donor Ag-pulsed DCreg rejected its graft in association with progressively elevated anti-donor Ab, 525 days post-transplant (160 days after withdrawal of immunosuppression). These findings indicate a modest but not statistically significant beneficial effect of donor Ag-pulsed autologous DCreg infusion on NHP graft survival when administered with a minimal immunosuppressive drug regimen.

show abstract

“…In allotransplantation, IL‐17 can contribute to allograft rejection. Overall inflammation was reduced in IL‐17‐deficient mice (on a background of C57BL/6) after BALB/c lung transplantation and blockade of IL‐17 with IL‐17 antibodies also contributed to reduce inflammation in allograft recipients, which were consistent with the previous studies …”

Section: Potential Pathological Role Of Il‐17 In Xenotransplantationmentioning

confidence: 99%

Potential pathological role of pro‐inflammatory cytokines (IL‐6, TNF‐α, and IL‐17) in xenotransplantation

Zhao

Cooper

Wang

et al. 2019

Xenotransplantation

View full text Add to dashboard Cite

show abstract

IL-17 Deficiency Attenuates Allograft Injury and Prolongs Survival in a Murine Model of Fully MHC-Mismatched Renal Allograft Transplantation

Cited by 34 publications

References 49 publications

RETRACTED ARTICLE: Approaching treatment for immunological rejection of living-donor liver transplantation in rats

RETRACTED ARTICLE: Approaching treatment for immunological rejection of living-donor liver transplantation in rats

Renal Allograft Survival in Nonhuman Primates Infused With Donor Antigen-Pulsed Autologous Regulatory Dendritic Cells

Potential pathological role of pro‐inflammatory cytokines (IL‐6, TNF‐α, and IL‐17) in xenotransplantation

Contact Info

Product

Resources

About