Targetting Monocytes With Microparticles To Prevent Kidney Allograft Rejection
Funder
National Health and Medical Research Council
Funding Amount
$967,005.00
Summary
Whilst transplantation is lifesaving for many Australians with organ failure, it is a treatment rather than cure as recipients are dependent upon lifelong immunosuppression to prevent transplant rejection. Risks of death due to infection and cancer therefore remain high. We will test a new strategy in mice which modifies recipients of monocytes at the time of transplantation, to enable them to accept and tolerate the organ without ongoing need for expensive and dangerous immunosuppressive drugs.
TOLERANCE OR REJECTION – THE ROLE OF INNATE IMMUNITY IN DETERMINNG THE FATE OF A KIDNEY ALLOGRAFT
Funder
National Health and Medical Research Council
Funding Amount
$506,413.00
Summary
Transplantation is the optimal management for people with organ failure. Tolerance, to retain transplant function without immunosuppression, remains the key goal but is seldom achieved. We propose to block Toll-like receptor signalling to achieve kidney transplant tolerance in mice. If successful, we would translate this into clinical trials in human, seeking to achieve organ transplantation without the risks of cancer, infection and premature death that are currently faced by organ recipients.
Conquering The Final Frontier In Lung Transplantation - Mesenchymal Stromal Cell Therapy For Chronic Lung Allograft Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$1,887,790.00
Summary
Lung transplantation remains the only treatment option for an increasing number of Australians with end-stage lung disease, however long-term outcomes are severely compromised by the almost universal development of chronic rejection. Mesenchymal stromal cells (MSCs) hold great promise in treating rejection, and in a world-first we have recently demonstrated that this approach is safe. In another world-first, this randomized, controlled study will determine whether MSC therapy is effective.
Mechanisms Of Islet Graft Rejection And Acceptance
Funder
National Health and Medical Research Council
Funding Amount
$602,501.00
Summary
Islet grafts offer diabetic patients the promise of a return to insulin-independence. In this project we will study how natural regulatory T cells suppress islet graft rejection in a mouse model. We will determine where regulatory T cells interact with graft-rejecting T cells, and define the mechanisms used to mediate their suppressive effects. Our findings will aid in developing new ways to induce long-term acceptance of islet grafts without immunosuppressive drugs.
IL-6 As The Key Inflammatory Mediator Controlling GVHD
Funder
National Health and Medical Research Council
Funding Amount
$592,049.00
Summary
Allogeneic haematopoietic stem cell transplantation (SCT) is a curative treatment for blood cancers. Graft-versus-host disease (GVHD) is a major limitation which occurs when the newly transplanted immune system mounts a rejection response against the recipient and is responsible for the death of up to 40% of transplant recipients. These studies will optimize a new approach to prevent GVHD focusing on a protein called interleukin-6. Ultimately, it is anticipated such approaches will improve the o ....Allogeneic haematopoietic stem cell transplantation (SCT) is a curative treatment for blood cancers. Graft-versus-host disease (GVHD) is a major limitation which occurs when the newly transplanted immune system mounts a rejection response against the recipient and is responsible for the death of up to 40% of transplant recipients. These studies will optimize a new approach to prevent GVHD focusing on a protein called interleukin-6. Ultimately, it is anticipated such approaches will improve the overall survival of patients with blood cancers.Read moreRead less
Applying Quantitative Immunology To The Analysis Of Complex Genetic Diseases
Funder
National Health and Medical Research Council
Funding Amount
$864,596.00
Summary
The immune response of each individual varies. For some, the response invoked by foreign challenge is weak, leading to a lifetime of difficulty with infection. For others, the response is stronger, yielding excellent immunity, but opening the potential for overactive responses to self-material and autoimmune disease. We have a new theory for how the health of our immune system can be measured and we aim to apply it to understand the genesis of the many different forms of human immune diseases.
Dynamics And Mechanisms Of Immune Complex-mediated Skin Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$526,467.00
Summary
Type III hypersensitivity underlies a number of common autoimmune diseases, including rheumatoid arthritis and lupus erythematosus. These diseases are caused by the deposition of immune complexes (IC) and the accumulation of neutrophils within small blood vessels. We will use real time imaging to dissect in space and time the recruitment of neutrophils and IC deposition during type III hypersensitivity reactions in order to better understand the pathogenesis of these conditions.
The Axis Of Bcl-2, Plasmacytoid DCs And Lupus As A Basis For Therapy
Funder
National Health and Medical Research Council
Funding Amount
$712,172.00
Summary
Systemic lupus erythematosus (SLE) affects 1 in 1000 Australians, mostly women. Here the immune system goes awry and makes antibodies against the body’s own components including the body’s DNA. This leads to damage to many parts of the body including kidneys, joints, brain and heart. It is incurable. A particular immune cell controls the development of this disease and we have found this cell is selectively killed by an inexpensive drug, which we hope will be a better way of treating SLE.
Analysis Of Antigen Receptor Sharing By T And B Lymphocytes
Funder
National Health and Medical Research Council
Funding Amount
$540,356.00
Summary
To survive an infection the immune system must rapidly expand the number of immune cells that have pathogen-specific receptors that recognise, and therefore specifically combat, the infection. This normally occurs through proliferation of the immune cells. We have found that in addition to proliferation, the number of cells with these receptors can be increased by a process of receptor transfer between cells. This grant aims to further advance our understanding of this novel phenomenon.
Determining The Role Of DOCK8 In CD4+ T And B Cell Differentiation And Its Implications On Autosomal Recessive Hyper IgE Syndrome (AR-HIES)
Funder
National Health and Medical Research Council
Funding Amount
$512,600.00
Summary
Autosomal recessive hyper IgE (AR-HIES) syndrome due to mutations in DOCK8 is a rare primary immunodeficiency whereby patients present with susceptibility to severe and recurrent viral infections as well as an increased risk of developing cancer, severe food and environmental allergies, and atopic disease characterised by hyper IgE and extreme eosinophilia. This grant will investigate how abnormal DOCK8 function in CD4+ T cells and B cells contributes to disease pathogenesis in AR-HIES patients.