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Cellular and Molecular Immune Research on Renal Transplantation

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 2459

Special Issue Editor


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Guest Editor
Nuffield Department of Surgical Sciences, Oxford Transplant Centre, Churchill Hospital, University of Oxford, Oxford OX3 7LJ, UK
Interests: kidney transplantation; kidney ischemia reperfusion injury

Special Issue Information

Dear Colleagues,

We are pleased to announce the upcoming special issue focusing on cellular and molecular immune research in Renal Transplantation.

Although kidney transplantation offers the best long-term outcome for patients with kidney failure there are still many patients on the waiting list who never receive an organ. In the past 10 years, the population of organ donors has shifted towards older individuals with co-morbidities such as hypertension, cardiac disease and diabetes. This has resulted in higher rates of organ decline to avoid poor short and long term function and created uncertainty about which organs are suitable for transplant. There is a growing need to better understand the cellular and molecular fingerprint of donor organs to help select appropriate organs for transplant and understand the mechanisms of decline after transplant.

Recent developments in the field include the assessment of donor organs using technology such as machine perfusion, which has also created a platform for the delivery of cell and immune therapies and drugs. Novel techniques of biological sample analysis using transcriptomics, proteomics and single cell analysis are also exciting areas of development. This special issue will showcase the latest research in cellular and molecular aspects of kidney transplantation including experimental models, animal studies and cell culture. We warmly welcome the submission of short communications, original research articles, clinical trials and review articles.

This special issue is supervised by Dr. James P. Hunter and assisted by our Topical Advisory Panel Member Dr. Letizia Lo Faro(University of Oxford Medical Sciences Division, Oxford, United Kingdom). We warmly welcome the submission of short communications, original research articles, clinical trials and review articles.

Dr. James P. Hunter
Guest Editor

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Keywords

  • kidney transplantation
  • cell therapy
  • molecular biology
  • ischaemia-reperfusion
  • machine perfusion

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Published Papers (1 paper)

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Research

18 pages, 2915 KiB  
Article
Dissecting the Therapeutic Mechanisms of Sphingosine-1-Phosphate Receptor Agonism during Ischaemia and Reperfusion
by Georgina C. Wilkins, Jenny Gilmour, Eirini Giannoudaki, John A. Kirby, Neil S. Sheerin and Simi Ali
Int. J. Mol. Sci. 2023, 24(13), 11192; https://doi.org/10.3390/ijms241311192 - 7 Jul 2023
Cited by 4 | Viewed by 1975
Abstract
Sphingosine 1-phosphate (S1P) and S1P receptors (S1PR) regulate many cellular processes, including lymphocyte migration and endothelial barrier function. As neutrophils are major mediators of inflammation, their transendothelial migration may be the target of therapeutic approaches to inflammatory conditions such as ischaemia–reperfusion injury (IRI). [...] Read more.
Sphingosine 1-phosphate (S1P) and S1P receptors (S1PR) regulate many cellular processes, including lymphocyte migration and endothelial barrier function. As neutrophils are major mediators of inflammation, their transendothelial migration may be the target of therapeutic approaches to inflammatory conditions such as ischaemia–reperfusion injury (IRI). The aim of this project was to assess whether these therapeutic effects are mediated by S1P acting on neutrophils directly or indirectly through the endothelial cells. First, our murine model of peritoneum cell recruitment demonstrated the ability of S1P to reduce CXCL8-mediated neutrophil recruitment. Mechanistic in vitro studies revealed that S1P signals in neutrophils mainly through the S1PR1 and 4 receptors and induces phosphorylation of ERK1/2; however, this had no effect on neutrophil transmigration and adhesion. S1P treatment of endothelial cells significantly reduced TNF-α-induced neutrophil adhesion under flow (p < 0.01) and transendothelial migration towards CXCL8 during in vitro chemotaxis assays (p < 0.05). S1PR1 agonist CYM5442 treatment of endothelial cells also reduced neutrophil transmigration (p < 0.01) and endothelial permeability (p < 0.005), as shown using in vitro permeability assays. S1PR3 agonist had no effects on chemotaxis or permeability. In an in vivo mouse model of renal IRI, S1PR agonism with CYM5442 reduced endothelial permeability as shown by reduced Evan’s Blue dye extravasation. Western blot was used to assess phosphorylation at different sites on vascular endothelial (VE)–cadherin and showed that CYM5442 reduced VEGF-mediated phosphorylation. Taken together, the results of this study suggest that reductions in neutrophil infiltration during IRI in response to S1P are mediated primarily by S1PR1 signalling on endothelial cells, possibly by altering phosphorylation of VE–cadherin. The results also demonstrate the therapeutic potential of S1PR1 agonist during IRI. Full article
(This article belongs to the Special Issue Cellular and Molecular Immune Research on Renal Transplantation)
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