Transforming growth factor β1 and Fas ligand synergistically enhance immune tolerance in dendritic cells in liver transplantation

Qiu, Minglian; Chen, Yujuan; Zeng, Jinhua; Liu, Jingfeng

doi:10.1016/j.jss.2017.05.040

Cited by 12 publications

(15 citation statements)

References 33 publications

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“…Mono-DC cotransfected with TGF-β1/Fas-L could prolong the survival time in murine liver transplantation. The increased level of Fas-L could induce T cell apoptosis ( 84 ). Immature DC transduced by lentiviral vectors expressing human IL-10 and FasL genes could significantly reduce the expression of costimulatory molecules and T cell proliferation and extend the survival period of rat liver allografts ( 94 ).…”

Section: The Function Of Tol-dcmentioning

confidence: 99%

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Tolerogenic Dendritic Cells: The Pearl of Immunotherapy in Organ Transplantation

et al. 2020

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Over a half century, organ transplantation has become an effective method for the treatment of end-stage visceral diseases. Although the application of immunosuppressants (IS) minimizes the rate of allograft rejection, the common use of IS bring many adverse effects to transplant patients. Moreover, true transplant tolerance is very rare in clinical practice. Dendritic cells (DCs) are thought to be the most potent antigen-presenting cells, which makes a bridge between innate and adaptive immunity. Among their subsets, a small portion of DCs with immunoregulatory function was known as tolerogenic DC (Tol-DC). Previous reports demonstrated the ability of adoptively transferred Tol-DC to approach transplant tolerance in animal models. In this study, we summarized the properties, ex vivo generation, metabolism, and clinical attempts of Tol-DC. Tol-DC is expected to become a substitute for IS to enable patients to achieve immune tolerance in the future.

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Section: The Function Of Tol-dcmentioning

confidence: 99%

“…DC cotransfected with plasmids encoding TGF-β and FasL show low expression of CD85 and CD80. These Tol-DC decrease Banff rejection activity index and allow graft function recovery in rat liver grafts, which is correlated to the increased expression of IL-10 and decreased expression of IL-1 and IL-12 ( 103 ).…”

Section: The Function Of Tol-dcmentioning

confidence: 99%

Tolerogenic Dendritic Cells: The Pearl of Immunotherapy in Organ Transplantation

et al. 2020

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“…DCs, professional antigen‐presenting cells, induce and maintain immune tolerance, and thus have been modified by drug treatment or genetic modification to create tolerogenic DCs that can be used for immune therapy. Anti‐inflammatory and immunosuppressive factors such as IL‐10, TGF‐β1, FasL and vitamin D3 metabolites produced by genetic modification inhibited the expression of costimulatory molecules and enhanced the tolerogenic potential of DCs to block their maturation and maintain them at the immature stage . Gene‐modified DCs can induce regulatory T cells and promote transplant‐tolerance after allogeneic transplantation .…”

Section: Discussionmentioning

confidence: 99%

“…ImDCs, derived from bone marrow cells of Lewis rats ( n = 10), were prepared as previously described . In brief, bone marrow cells from the bilateral tibia and fibula were flushed out with 5 mL RPMI 1640 medium (61870044; Gibco, Langley, CA, USA), mixed with 5 mL lymphocyte separation medium (LTS1083P; TBD, Tianjin, China) and centrifuged at 5000 g for 20 min.…”

Section: Methodsmentioning

confidence: 99%

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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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Liver DCs in health and disease

Wirtz

Brandt

Berres

2019

International Review of Cell and Molecular Biology

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Transforming growth factor β1 and Fas ligand synergistically enhance immune tolerance in dendritic cells in liver transplantation

Abstract: By enhancing immune tolerance, reducing liver damage, and achieving long-term postsurgery survival, TGF-β1/FasL cotransfection of imDCs may prove more beneficial for patients undergoing liver transplantation.

Cited by 12 publications

References 33 publications

Tolerogenic Dendritic Cells: The Pearl of Immunotherapy in Organ Transplantation

Tolerogenic Dendritic Cells: The Pearl of Immunotherapy in Organ Transplantation

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

Liver DCs in health and disease

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