The Role Of NF-?B Transcription Factor RelA In Regulatory T Cell Homeostasis And Function
Funder
National Health and Medical Research Council
Funding Amount
$637,114.00
Summary
Treg cells constitute an immune regulatory cell population that is essential for the prevention of fatal autoimmunity; however, they also limit immunity against cancer. We have discovered that the factor RelA is of critical importance for Treg development and function. We now aim to illuminate the functions of RelA in detail. Understanding the molecules that impact on Treg cell biology is critical to harness their potential for clinical intervention such as treatment of autoimmunity and cancer.
How Does NF-kB2 Regulate Thymic Selection To Prevent Organ-specific Autoimmune Disease?
Funder
National Health and Medical Research Council
Funding Amount
$787,600.00
Summary
Autoimmune diseases like type 1 diabetes and thyroiditis arise from defects that cause the immune system to confuse self and non-self. Normally, this distinction is programmed in the thymus. We recently identified the gene that causes a form of autoimmune disease. We also made an important discovery about how the thymus gland regulates self-non-self discrimination. We will build on these two discoveries to gain a precise understanding of how the immune system normally avoids autoimmune disease.
Evolution Of Adaptive Immunity To Gluten In Coeliac Disease.
Funder
National Health and Medical Research Council
Funding Amount
$472,034.00
Summary
Coeliac disease affects 1 in 100 Australians and can cause significant health problems. Under-diagnosis and a difficult, costly treatment (lifelong gluten free diet) are serious clinical issues. The feasibility of simpler diagnostics and therapies in children and adults for coeliac disease depends on whether children and adults react in the same way to gluten. This proposal seeks to determine whether the immune response to gluten changes over time and establish the feasibility of peptide-based a ....Coeliac disease affects 1 in 100 Australians and can cause significant health problems. Under-diagnosis and a difficult, costly treatment (lifelong gluten free diet) are serious clinical issues. The feasibility of simpler diagnostics and therapies in children and adults for coeliac disease depends on whether children and adults react in the same way to gluten. This proposal seeks to determine whether the immune response to gluten changes over time and establish the feasibility of peptide-based applications.Read moreRead less
A Novel Role For The IL-2 Pathway In Type-1-diabetes.
Funder
National Health and Medical Research Council
Funding Amount
$548,548.00
Summary
Genes encoding IL-2 and its receptor are strongly linked to susceptibility to multiple autoimmune diseases, including type-1-diabetes. Despite the importance of this pathway in the immune system, it is not yet understood how the associated genes affect disease. In this study, a novel function for IL-2 expression by dendritic cells in normal self-tolerance is investigated. The impacts of dendritic cell produced IL-2 expression and linkage to autoimmunity will be elucidated in both mouse and man.
The Molecular Basis Of Human CD4+ T-cell Responses In Autoimmune Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$656,498.00
Summary
Over 120,000 Australians currently suffer from type 1 diabetes. This incurable disease typically strikes in childhood or adolescence and is caused by the immune system destroying the cells which make insulin. This project aims to determine how and why the insulin producing cells are recognized by the immune system. Eventually this work will lead to new vacccines to prevent the immune system from destroying the insulin producing cells.
Prevention Of Autoimmune Diabetes By Immune Tolerance To Proinsulin
Funder
National Health and Medical Research Council
Funding Amount
$504,597.00
Summary
In type 1 diabetes, insulin is the first target of the immune system. Strategies to prevent the immune system targeting insulin in mice early in the disease process work, but it is not clear if such strategies would be effective if applied late. This is important because preventive therapies for human type 1 diabetes are currently feasible only late in the disease process. We aim to address this by removing T cells specific for insulin at different stages of the disease.
How Deletional And Non-Deletional Tolerance Mechanisms Integrate To Prevent Autoimmune Disease
Funder
National Health and Medical Research Council
Funding Amount
$509,944.00
Summary
The body produces millions of immune cells every day to fight infection. Some of these immune cells are defective and dangerous because they can cause autoimmune diseases, like Type I diabetes and multiple sclerosis. To defuse this risk, such immune cells are either caused to die or are inactivated to prevent autoimmunity. We propose to investigate how the processes of immune cell death and inactivation work in health and disease so we may harness these mechanisms to cure autoimmunity.
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.
The Role Of The T Cell Protein Tyrosine Phosphatase In Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$654,725.00
Summary
Autoimmune diseases such as type 1 diabetes, Crohns disease & rheumatoid arthritis collectively affect ~5% of Australians & are associated with the immune system attacking the body’s organs as if they were a foreign infection. Genetic studies in humans & animal studies point towards the enzyme TCPTP being important in the prevention of autoimmunity. This proposal will define the molecular & cellular pathways by which TCPTP prevents autoimmunity.
Analysis Of Human CD4+ T-cell Responses To Epitopes Formed By Peptide Fusion In The Pathogenesis Of Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$1,239,989.00
Summary
Type 1 diabetes is caused by immune-mediated destruction of the insulin-secreting beta cells. Recently we discovered new targets ‘seen’ by the immune system that may explain why the immune system causes type 1 diabetes. Here we will determine if responses to these targets cause type 1 diabetes. This is important because it tests a new idea and our results will have a major impact on efforts to develop new therapies for type 1 diabetes an other autoimmune diseases.