Gamma-Delta Tregs, CD8 Tregs And Selected Natural Tregs To Treat Renal Injury
Funder
National Health and Medical Research Council
Funding Amount
$605,096.00
Summary
Chronic kidney disease (CKD) progresses due to ongoing damage to the kidney. We have identified three types of white cells that can reduce kidney damage in CKD. The first is a unique set of gamma-delta T cells that expand in the kidney and protect against injury. The second is a restricted set of CD8 T cell that can protect against kidney injury. The third are targeted natural regulatory T cells. These studies develop each of these three subsets as potential cellular therapies in CKD.
EFFECTOR AND REGULATORY INTERSTITIAL INFLAMMATORY CELLS IN CHRONIC PROTEINURIC RENAL DISEASE
Funder
National Health and Medical Research Council
Funding Amount
$289,150.00
Summary
Current treatments for chronic kidney disease are ineffective. As a consequence, kidney failure progresses to the stage where patients require dialysis or transplantation to remain alive. Every year almost 1600 Australians commence dialysis for this reason, and many more die of kidney failure or its complications. This project will lead to a greater understanding of why kidney failure progresses, and will define more effective treatments for preventing progression. In progressive chronic kidney ....Current treatments for chronic kidney disease are ineffective. As a consequence, kidney failure progresses to the stage where patients require dialysis or transplantation to remain alive. Every year almost 1600 Australians commence dialysis for this reason, and many more die of kidney failure or its complications. This project will lead to a greater understanding of why kidney failure progresses, and will define more effective treatments for preventing progression. In progressive chronic kidney diseases of all types, the supporting tissue within the kidney (the interstitium) becomes infiltrated with inflammatory cells. The amount of interstitial inflammation has an important bearing on the severity of kidney failure, and the rate at which kidney disease progresses to endstage. The reasons that these inflammatory cells infiltrate the interstitium, and their exact role in the progression of kidney disease are only partially understood. For example, some of these inflammatory cells appear to cause kidney scarring, whereas others appear to be protective. Moreover, even though they are obvious targets for treatment aimed at slowing the progression of kidney disease, current treatments are largely ineffective as they do not differentiate between the different types of inflammatory cells, and whether these cells are causing or preventing damage. Our laboratory has recently developed a robust model of chronic kidney disease, which will be used to examine the effect of individual types of interstitial inflammatory cells on the progression of kidney disease. So far we have shown that depletion of one type of inflammatory cell (CD4 lymphocytes) worsened the disease process, whereas depletion of two other cell types (CD8 lymphocytes or macrophages) was protective. This raises the real and exciting possibility that treatment directed against specific inflammatory cells may be effective in the treatment of progressive kidney disease in humans.Read moreRead less
Targeting The Pathophysiology And Therapy Of Liver Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$484,006.00
Summary
Hepatic fibrosis, or scarring of the liver, is a serious condition which can lead to liver cancer or death. Treatment of liver scarring is currently not effective once the scarring is well developed. This project aims to examine agents which may act to halt liver scarring once it has already developed. Outcomes from this project may help provide potential treatments to reduce the need for liver transplantation or to reduce patient deaths.
Identifying Donor And Recipient Gene Pathways In Renal Transplant Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$1,082,069.00
Summary
We have identified a 13 gene set that predicts renal transplant fibrosis and graft loss in patients. Interestingly some of these gene are donor as well as recipient related. In this project we aim to investigate these gene pathways in cell lines and animal models to better understand how the cause of renal fibrosis after transplantation.
Treatment Of Diverse Renal Diseases With Regulatory Cells
Funder
National Health and Medical Research Council
Funding Amount
$566,946.00
Summary
Chronic kidney disease (CKD) is a major cause of death and disability in the Australian population. Current treatments for CKD are non-specific and frequently ineffective. As a consequence, kidney failure progresses to the stage where patients require dialysis or tranplantation to remain alive. Every year more than 1700 Australians require kidney replacement therapy for this reason and many more die of kidney failure or its complications. Some forms of kidney disease are self-limited whereas oth ....Chronic kidney disease (CKD) is a major cause of death and disability in the Australian population. Current treatments for CKD are non-specific and frequently ineffective. As a consequence, kidney failure progresses to the stage where patients require dialysis or tranplantation to remain alive. Every year more than 1700 Australians require kidney replacement therapy for this reason and many more die of kidney failure or its complications. Some forms of kidney disease are self-limited whereas others are characterised by chronic kidney scarring and the eventual development of endstage disease. This project will explore whether natural protective cells (regulatory T cells) can be used to treat differing types of CKD, including those characterised predominantly by inflammation or by fibrosis. In addition, the protective mechanisms of regulatory T cells (including their interaction with resident kidney cells) will be explored, as will ways of increasing the efficacy of regulatory T cell therapy.Read moreRead less