Effects of IL‐10‐ and FasL‐overexpressing dendritic cells on liver transplantation tolerance in a heterotopic liver transplantation rat model
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 g...
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Published in: | Immunology and cell biology Vol. 97; no. 8; pp. 714 - 725 |
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Main Authors: | , , , , , , , |
Format: | Journal Article |
Language: | English |
Published: |
United States
Blackwell Science Ltd
01-09-2019
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Subjects: | |
Online Access: | Get full text |
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Summary: | 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.
Immature dendritic cells (imDCs) derived from donors were transduced by lentiviral vectors expressing human (h)IL‐10 and/or hFasL gene, and were intraperitoneally injected into recipient rats as a model of liver transplantation (LT) to examine the rejection grade, liver functions (ALT, AST and TBIL) and post‐transplant survival. The findings demonstrated that the transfusion of IL‐10‐FasL/imDCs enhanced immune tolerance and prolonged the survival of liver allografts after LT. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0818-9641 1440-1711 |
DOI: | 10.1111/imcb.12252 |