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.
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.
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.
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.
De Novo Mutations And The Pathogenesis Of Childhood-onset Autoimmune Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,406,510.00
Summary
This project aims to reveal the gene abnormalities that cause devastating autoimmune diseases to develop in some children, such as Type 1 diabetes, juvenile arthritis and autoimmune destruction of blood cells. The project will use new technologies to identify alterations in the DNA sequence of a child compared to either of their parents, and to test suspicious DNA alterations in laboratory mice in order to understand the gene effects and evaluate new 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.
How Does Genetic Variation For Trig Affect Autoimmune Responses Mediated By Toll-like Receptors?
Funder
National Health and Medical Research Council
Funding Amount
$671,114.00
Summary
Juvenile diabetes is an autoimmune disease that affects more than 120,000 Australians. We have recently discovered a novel gene, named Trig, in a genetic study of mice that develop juvenile diabetes similar to children. This research proposal aims to determine the function of Trig in the immune system and how it contributes to the development of autoimmune diseases, such as juvenile diabetes.