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.
T Helper Cytokines In Immunity And Organ-specific Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$443,946.00
Summary
The overall goal of these studies is to identify mechanisms underlying the effects of cytokines on T cell-mediated immunity, how defects in these processes can result in organ specific autoimmune disease, and whether exploiting these mechanisms may result in improved therapies for individuals with autoimmune diseases. The proposed aims build on my previous work on interleukin-21 and interleukin-21-producing T helper cells in both immunity and autoimmunity.
The Role Of Interleukin (IL)-27 In The Germinal Centre Reaction During Normal And Autoimmune Responses
Funder
National Health and Medical Research Council
Funding Amount
$476,226.00
Summary
Protective immune responses depend on supportive interactions between different white blood cell types. Signalling proteins called _cytokines� are a key means of communication between cells. Abnormal cytokine production can lead to poor protection against infection or immune attack against the tissues (ie. autoimmune disease). This project aims to determine the importance of one such cytokine, called IL-27, in the production of antibodies in normal immune responses as well as in autoimmune disea ....Protective immune responses depend on supportive interactions between different white blood cell types. Signalling proteins called _cytokines� are a key means of communication between cells. Abnormal cytokine production can lead to poor protection against infection or immune attack against the tissues (ie. autoimmune disease). This project aims to determine the importance of one such cytokine, called IL-27, in the production of antibodies in normal immune responses as well as in autoimmune diseases like Lupus.Read moreRead less
An estimated 5 million patients worldwide suffer from the autoimmune disease and in Australia and New zealand, autoimmune diseases affect around 1 in 20 people.Our research will investigate patients samples and animal models to identify the pathogenesis of autoimmune disease and establish new monitor systems and better therapeutic treatments of autoimmune diseases.
Organ-specific Autoimmunity: The Role Of The Thymus And Periphery In Shaping The Gastric-specific T Cell Repertoire
Funder
National Health and Medical Research Council
Funding Amount
$579,763.00
Summary
The immune system normally protects against invasion by pathogens such as harmful viruses and bacteria. In autoimmune diseases the same mechanisms that are used to protect us are erroneously targeted to our own tissues. White blood cells, called T lymphocytes are responsible for attacking our own tissues in autoimmune diseases. Our studies will employ a range of molecular, genetic and imaging technologies to track the rare and potential harmful white blood cells. Our studies should reveal the me ....The immune system normally protects against invasion by pathogens such as harmful viruses and bacteria. In autoimmune diseases the same mechanisms that are used to protect us are erroneously targeted to our own tissues. White blood cells, called T lymphocytes are responsible for attacking our own tissues in autoimmune diseases. Our studies will employ a range of molecular, genetic and imaging technologies to track the rare and potential harmful white blood cells. Our studies should reveal the mechanisms by which these self destructive T lymphocytes are silenced in healthy individuals on the one hand, and on the other hand escape to cause destruction in individuals with autoimmune diseases. This fundamental information will allow the development of therapeutic strategies to selectively turn-off these destructive T lymphoctyes in individuals with autoimmune disease and thereby remove the damaging immune response and cure the disease.Read moreRead less
The Molecular Determinants Of Immunological Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$473,477.00
Summary
Autoimmune diseases, such as type I diabetes and multiple sclerosis, are debilitating disorders that impose a massive toll on wellbeing in Australia and worldwide. This fellowship will support research aimed at determining the genes and mechanisms that control autoimmunity. New technologies will be brought to bear to track immune cells throughout their development, maturity and malfunction in disease settings. We aim to uncover new therapeutic targets to prevent and reverse autoimmune disease.
The Role Of Interleukin-21 In The Pathogenesis Of Autoimmune Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$519,000.00
Summary
T cells are a component of our blood (white blood cells) and a major component of the body's defense system against infection, known as immunity. Without T cells, we would fail to resist infection by foreign agents, such as viruses, bacteria and fungi. Autoimmune (type 1) diabetes is a disease in which T cells attack our own pancreatic islet self tissues as if they were foreign. T cells that react against the islets of the pancreas cause destruction of the insulin producing beta cells so that th ....T cells are a component of our blood (white blood cells) and a major component of the body's defense system against infection, known as immunity. Without T cells, we would fail to resist infection by foreign agents, such as viruses, bacteria and fungi. Autoimmune (type 1) diabetes is a disease in which T cells attack our own pancreatic islet self tissues as if they were foreign. T cells that react against the islets of the pancreas cause destruction of the insulin producing beta cells so that the pancreas can no longer make insulin. Diabetes is a life-threatening disease because insulin is a hormone that enables people to get energy from food. Type 1 diabetes is usually diagnosed in childhood and insulin must be administered daily by injection or through a pump in order to survive. Unfortunately, taking insulin doesn t cure diabetes and people continue to suffer from an extensive list of complications affecting most vital organs. Interleukin-21 (IL-21) is a soluble protein that is produced by cells enabling them to communicate with other cells. IL-21 helps cells to produce factors that cause inflammation and assist in clearance of viruses and bacteria from the body. However, our studies show that IL-21 is a major factor in the development of the T cells that destroy beta cells and cause diabetes. Our studies show that IL-21 is over-expressed in an important murine model of spontaneous type-1 diabetes. We have isolated the T cells that cause diabetes and show that they are distinguished from other T cells by very high levels of the receptor for IL-21. This project focuses on the IL-21-responsive T cells that cause diabetes and aims to determine the mechanisms by which the cytokine IL-21 causes destructive immune responses and ways to modulate its production. This project applies basic science to the important public health issue of type 1 diabetes for the development of therapeutic intervention strategies.Read moreRead less
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.