Please use this identifier to cite or link to this item:
https://wslhd.intersearch.com.au/wslhdjspui/handle/1/7271
Title: | Tolerogenic dendritic cells protect against acute kidney injury |
Authors: | Li, Jennifer;Robertson, Harry;Trinh, Katie;Raghubar, A. M.;Nguyen, Q.;Matigian, N.;Patrick, E.;Thomson, A. W.;Mallett, A. J.;Rogers, Natasha M. |
WSLHD Author: | Li, Jennifer;Robertson, Harry;Trinh, Katie;Rogers, Natasha M. |
Issue Date: | 2023 |
Citation: | Kidney International 2023 |
Abstract: | Ischemia reperfusion injury is a common precipitant of acute kidney injury that occurs following disrupted perfusion to the kidney. This includes blood loss and hemodynamic shock, as well as during retrieval for deceased donor kidney transplantation. Acute kidney injury is associated with adverse long-term clinical outcomes and requires effective interventions that can modify the disease process. Immunomodulatory cell therapies such as tolerogenic dendritic cells remain a promising tool, and here we tested the hypothesis that adoptively transferred tolerogenic dendritic cells can limit kidney injury. The phenotypic and genomic signatures of bone marrow-derived syngeneic or allogeneic, Vitamin-D3/IL-10 conditioned tolerogenic dendritic cells were assessed. These cells were characterized by high PD-L1:CD86, elevated IL-10, restricted IL-12p70 secretion and a suppressed transcriptomic inflammatory profile. When infused systemically, these cells successfully abrogated kidney injury without modifying infiltrating inflammatory cell populations. They also provided protection against ischemia reperfusion injury in mice pre-treated with liposomal clodronate, suggesting the process was regulated by live, rather than reprocessed cells. Co-culture experiments and spatial transcriptomic analysis confirmed reduced kidney tubular epithelial cell injury. Thus, our data provide strong evidence that peri-operatively administered tolerogenic dendritic cells have the ability to protect against acute kidney injury and warrants further exploration as a therapeutic option. This technology may provide a clinical advantage for bench-to-bedside translation to affect patient outcomes. |
URI: | https://wslhd.intersearch.com.au/wslhdjspui/handle/1/7271 |
DOI: | https://dx.doi.org/10.1016/j.kint.2023.05.008 |
Journal: | Kidney International |
Type: | Journal Article |
Study or Trial: | Controlled Study |
Department: | Renal Medicine |
Facility: | Blacktown Westmead Auburn |
Affiliated Organisations: | Centre for Transplant and Renal Research, Westmead Institute for Medical Research, Westmead, NSW, Australia Sydney Medical School, Faculty of Health and Medicine, University of Sydney, Sydney, NSW, Australia School of Mathematics and Statistics, University of Sydney, Sydney, NSW, Australia Institute for Molecular Bioscience, the University of Queensland, Brisbane, QLD, Australia Queensland Cyber Infrastructure Foundation Bioinformatics, Brisbane, QLD, Australia Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA Department of Renal Medicine, Townsville University Hospital, Townsville, QLD, Australia College of Medicine and Dentistry, James Cook University, Townsville, QLD, Australia Department of Renal Medicine, Westmead Hospital, Westmead, NSW, Australia |
Keywords: | Tolerogenic acute kidney injury ischemia reperfusion injury kidney |
Appears in Collections: | Blacktown Mount Druitt Hospital |
Files in This Item:
There are no files associated with this item.
Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.