The Role Of Aire In Immunological Tolerance And Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$434,134.00
Summary
The immune system is designed to protect us from foreign pathogens such as bacteria, viruses and parasites. This is achieved through lymphocytes which recognise foreign pathogens. However in 5-6% of the population the immune system attacks the host and induces autoimmunity. We aim to understand the mechanisms which control the production of self-reacting lymphocytes and how we may reduce the incidence of autoimmunity.
Tolerogenic Dendritic Cells In Common Marmoset Renal Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$162,756.00
Summary
ORGAN TRANSPLANT PATIENTS currently need life-long immune suppressing drugs to prevent rejection, often using 15 medications a day, costing Australia $52M in 2002. These drugs increase risks of infection and cancer. 90% of patients develop some form of cancer over 30 years. They also cause non-specific side effects including high blood pressure, diabetes and osteoporosis. The average lifespan of a kidney transplant is 8-15 years. Major causes of kidney transplant loss are rejection and drug toxi ....ORGAN TRANSPLANT PATIENTS currently need life-long immune suppressing drugs to prevent rejection, often using 15 medications a day, costing Australia $52M in 2002. These drugs increase risks of infection and cancer. 90% of patients develop some form of cancer over 30 years. They also cause non-specific side effects including high blood pressure, diabetes and osteoporosis. The average lifespan of a kidney transplant is 8-15 years. Major causes of kidney transplant loss are rejection and drug toxicity. TRANSPLANTS ARE REJECTED when a recipient's immune system sees the kidney as foreign. Immune suppressing drugs prevent rejection by stopping the reaction to foreign tissues, but this causes increased infection and cancer risk. IMMUNE TOLERANCE means the recipient's immune system sees a transplant not as foreign but as part of itself, no longer reacting to it. If tolerance could be achieved for transplants, patients wouldn't need to use immune suppressing drugs. Costs of immune suppression would be nil. Tolerance is the best long-term solution for patients needing transplants. Tolerance has been achieved in various ways in mice models. DENDRITIC CELLS can be used to induce tolerance as they can silence a recipient's immune system, preventing it from seeing transplant tissues as foreign. We have shown in mice that a single infusion of a certain type of dendritic cells caused prolonged transplant tolerance without needing immune suppression. This project aims to use dendritic cells to induce tolerance in a marmoset model - a required step before allowing this therapy to be done in humans. PRIMATES like MARMOSETS have close genetic identity to humans and are ideal transplant models as their immune systems react much more like humans than other animals. Marmosets are not an endangered species and are smaller, cheaper and easier to care for than other primates. Ultimately, experiments in other species would need repeating in primates before human trials could be done.Read moreRead less
Inflammatory diseases, such as autoimmune diseases, result from an overactive immune system. A new therapy that is currently under trial is the use of special blood cells, called Treg cells, whose function is to suppress unwanted immune responses. This application evaluates the efficacy and safety of such treatments.
Tolerogenic Dendritic Cells In Kidney Transplantation: Studies In Common Marmoset Monkeys
Funder
National Health and Medical Research Council
Funding Amount
$124,014.00
Summary
Kidney transplantation is the preferred treatment for end-stage kidney disease, but requires immunosuppressive drugs to prevent transplant rejection. However, long-term immunosuppression can have toxic side effects and increase the risks of infection and cancer. This research examines the therapeutic potential of dendritic cells (a specialised immune cell-type) to promote tolerance of the transplant kidney, while enabling maintenance of normal immune function and avoidance of immunosuppression.
Understanding The Pathogenesis And Heterogeneity Of Autoimmunity As Failure Of Multiple Steps
Funder
National Health and Medical Research Council
Funding Amount
$504,023.00
Summary
Autoimmune diseases like diabetes, thyroid disease or rheumatoid arthritis affect around 1 in 15 people in Australia. It is clear that defects in a number of different genetic mechanisms can contribute to the development of autoimmunity. But it is currently not clear how these different mechanisms need to interact to prevent the onset of disease. This grant seeks to understand these interactions and how defects in two or more tolerance mechanisms can lead to autoimmunity.
Early Introduction Of Foods Into Infant Weaning Diets To Induce Oral Tolerance And Prevent Food Allergies.
Funder
National Health and Medical Research Council
Funding Amount
$143,660.00
Summary
Food allergies can be life threatening, and with no treatment, prevention is crucial. Traditional advice for babies whose parents have allergies has been to delay the introduction of allergy causing foods. However, recent research has questioned this approach. In this study I plan to investigate whether the early introduction of fish and eggs in the weaning diet can reduce the incidence of allergy. The results will be crucial to determine the best approach to reduce the risk of food allergy.
HLA-G/H2-Bl Is Critical For Regulating Inflammation In The Liver
Funder
National Health and Medical Research Council
Funding Amount
$494,050.00
Summary
The key factor to induction of liver fibrosis, progression to cirrhosis, and hepatocellular carcinoma is inflammation. Liver transplant and liver regeneration following liver resection are also dramatically impaired by elevation of inflammation. We have identified a potent anti-inflammatory protein, HLA-G, that is critical for regulating post-surgical inflammation in the liver. We will determine if HLA-G can reverse and/or block liver fibrosis and modify HLA-G for improved clinical potential.