Induction of Lymphocyte Apoptosis in Rat Liver Allograft by Adenoviral Gene Transfection of Human Interleukin-10

Li, Jiequn; Qi, Haiyun; He, Zhiwei; Hu, Wei; Si, Zhongzhou; Li, Yining

doi:10.1159/000276989

Cited by 6 publications

(4 citation statements)

References 63 publications

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“…Additionally, IL-10 has been shown to be upregulated in human livers [91] and kidneys [164]. Work undertaken by Li et al suggested that IL-10 expression after BD may be important in stimulating apoptosis of graft infiltrating lymphocytes through activation of the Fas/Fas Ligand pathway [165]. There is little published in the literature investigating the role of IL-5 and IL-13 during brain death.…”

Section: Stage Two Of Potential Organ Injury: Brain Deathmentioning

confidence: 99%

Inflammatory Signalling Associated with Brain Dead Organ Donation: From Brain Injury to Brain Stem Death and Posttransplant Ischaemia Reperfusion Injury

Watts

Thom

Fraser

2013

Journal of Transplantation

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Brain death is associated with dramatic and serious pathophysiologic changes that adversely affect both the quantity and quality of organs available for transplant. To fully optimise the donor pool necessitates a more complete understanding of the underlying pathophysiology of organ dysfunction associated with transplantation. These injurious processes are initially triggered by catastrophic brain injury and are further enhanced during both brain death and graft transplantation. The activated inflammatory systems then contribute to graft dysfunction in the recipient. Inflammatory mediators drive this process in concert with the innate and adaptive immune systems. Activation of deleterious immunological pathways in organ grafts occurs, priming them for further inflammation after engraftment. Finally, posttransplantation ischaemia reperfusion injury leads to further generation of inflammatory mediators and consequent activation of the recipient's immune system. Ongoing research has identified key mediators that contribute to the inflammatory milieu inherent in brain dead organ donation. This has seen the development of novel therapies that directly target the inflammatory cascade.

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Section: Stage Two Of Potential Organ Injury: Brain Deathmentioning

confidence: 99%

Inflammatory Signalling Associated with Brain Dead Organ Donation: From Brain Injury to Brain Stem Death and Posttransplant Ischaemia Reperfusion Injury

Watts

Thom

Fraser

2013

Journal of Transplantation

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“…IL‐10 produced by macrophages and Th2 cells has a crucial role in inducing immune tolerance via a variety of mechanisms including inhibiting the secretion of Th1 cell cytokines, and downregulating the expression of MHC II on monocytes and costimulatory molecules on macrophages. Based on these effects, IL‐10 is a candidate immunosuppressive cellular therapy for allograft rejection . In this study, imDCs produced IL‐10 themselves in vitro , and IL‐10 gene transduction boosted the production of IL‐10 more than four times.…”

Section: Discussionmentioning

confidence: 74%

Effects of IL‐10‐ and FasL‐overexpressing dendritic cells on liver transplantation tolerance in a heterotopic liver transplantation rat model

Zhang

Zhu

et al. 2019

Immunol Cell Biol

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Acute rejection is the major determinant for the long-term survival of donor liver after liver transplantation (LT). The aim of this study was to examine the therapeutic potential of interleukin (IL)-10-FasL-overexpressing immature dendritic cells (imDCs) to induce local immunosuppression in liver grafts. imDCs derived from donors were transduced by lentiviral vectors expressing human IL-10 and/or Fas ligand (FasL) gene(s), and the expression of surface molecules and the ability to induce T-cell proliferation were measured. imDCs were intraperitoneally injected into recipient rats as a model of LT to examine the rejection grade [Banff rejection activity index (RAI)], liver functions [Alanine aminotransferase, Aspartate aminotransferase (AST) and total bilirubin (TBIL)] and post-transplant survival. IL-10 and FasL co-transduction of imDCs induced a greater reduction in CD80, CD86 and major histocompatibility complex class II (MHC II) expression, as well as T-cell proliferation, but increased levels of IL-10 and FasL in culture supernatants compared with mono-transduced or untransduced imDCs (P < 0.05). The infusion of co-transduced imDCs in LT recipients reduced RAI scores, decreased plasma AST and TBIL, and prolonged survival compared with mono-transduced or untransduced imDC-treated liver allografts. These findings demonstrated that the transfusion of IL-10-FasL/imDCs enhanced immune tolerance and prolonged the survival of liver allografts after LT. The immunomodulatory activity of IL-10-and FasL-modified imDCs might be a new therapeutic approach to prevent organ rejection in clinical transplantation.

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“…The concept that exogenous IL-10 is useful therapeutically to diminish immunopathological disease has been previously examined in settings of transplantation and autoimmune disease (1,32,33). IL-10, delivered via adeno-associated virus or lentivirus vectors, diminishes the rate of graft rejection in several models of organ transplantation, including allogeneic heart, lung, liver, and pancreas transplants (8,11,19,25). IL-10 diminished disease severity in several autoimmune diseases, including mice with experimental autoimmune encephalomyelitis (EAE) (6,7,24,47).…”

Section: Discussionmentioning

confidence: 99%

Virally Expressed Interleukin-10 Ameliorates Acute Encephalomyelitis and Chronic Demyelination in Coronavirus-Infected Mice

Trandem

Jin

Weiss

et al. 2011

J Virol

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The absence of interleukin-10 (IL-10), a potent anti-inflammatory cytokine results in increased immune-mediated demyelination in mice infected with a neurotropic coronavirus (recombinant J2.2-V-1 [rJ2.2]). Here, we examined the therapeutic effects of increased levels of IL-10 at early times after infection by engineering a recombinant J2.2 virus to produce IL-10. We demonstrate that viral expression of IL-10, which occurs during the peak of virus replication and at the site of disease, enhanced survival and diminished morbidity in rJ2.2-infected wild-type B6 and IL-10 ؊/؊ mice. The protective effects of increased IL-10 levels were associated with reductions in microglial activation, inflammatory cell infiltration into the brain, and proinflammatory cytokine and chemokine production. Additionally, IL-10 increased both the frequency and number of Foxp3 ؉ regulatory CD4 T cells in the infected central nervous system. Most strikingly, the ameliorating effects of IL-10 produced during the first 5 days after infection were long acting, resulting in decreased demyelination during the resolution phase of the infection. Collectively, these results suggest that the pathogenic processes that result in demyelination are initiated early during infection and that they can be diminished by exogenous IL-10 delivered soon after disease onset. IL-10 functions by dampening the innate or very early T cell immune response. Further, they suggest that early treatment with IL-10 may be useful adjunct therapy in some types of viral encephalitis.

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Induction of Lymphocyte Apoptosis in Rat Liver Allograft by Adenoviral Gene Transfection of Human Interleukin-10

Cited by 6 publications

References 63 publications

Inflammatory Signalling Associated with Brain Dead Organ Donation: From Brain Injury to Brain Stem Death and Posttransplant Ischaemia Reperfusion Injury

Inflammatory Signalling Associated with Brain Dead Organ Donation: From Brain Injury to Brain Stem Death and Posttransplant Ischaemia Reperfusion Injury

Effects of IL‐10‐ and FasL‐overexpressing dendritic cells on liver transplantation tolerance in a heterotopic liver transplantation rat model

Virally Expressed Interleukin-10 Ameliorates Acute Encephalomyelitis and Chronic Demyelination in Coronavirus-Infected Mice

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