The Role Of Toll Like Receptors In Leukocyte Activation And Adherence In Glomeruli In Auto-immune Glomerulonephritis
Funder
National Health and Medical Research Council
Funding Amount
$82,554.00
Summary
1 in 7 Australians have Kidney disease. Kidney disease tends to be progressive and over 8500 Australians require renal replacement therapy (dialysis). The cost of dialysis from 2004-2010 in Australia will be $ 4.5 billion. Auto-immune disease and Diabetes accounts for nearly 60% of kidney failure. Whilst current regimes exist to treat Kidney disease these are limited because they are deleterious side-effects. Improved understanding of the mechanism of disease will lead to improved treatments.
Conversion And Function Of Regulatory T Cells In The Periphery: The Role Of The RelB Transcription Factor
Funder
National Health and Medical Research Council
Funding Amount
$526,878.00
Summary
There is limited understanding of the molecular mechanisms regulating immune tolerance, or protection from autoimmune diseases, like childhood diabetes. This proposal studies RelB-deficient mice. They present a novel opportunity to study tolerance and autoimmune disease development, as we have discovered that autoimmunity in these mice is correctable by treatment with dendritic cells expressing RelB. This may be relevant to treatment of patients with certain forms of autoimmune disease.
A T-cell Based Approach To Identifying Islet Antigens In Human Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$404,400.00
Summary
Autoimmune diseases arise when the immune system, which protects us from infections and cancer, attacks healthy tissues. Nobody knows why the immune system mistakes healthy for unhealthy tissue. The immune system's T cells are prime suspects because they play a central role in controlling the immune response. Hence, the aim of this work is to understand what human T cells see in healthy tissues that may lead them to cause autoimmune diseases like type 1 diabetes.
The Role Of Nalp1 In Autoimmune Disease And Innate Immune Defense As Determined By Murine Genetic Deletion.
Funder
National Health and Medical Research Council
Funding Amount
$320,237.00
Summary
The innate immune system is a critical barrier against invading microorganisms, however when improperly regulated it can lead to autoimmune disease. Nalp1 is a protein that is important for innate immune recognition of anthrax infection, and is also involved in susceptibility to vitiligo and associated autoimmune diseases. This project seeks to create mice that are deficient for the gene encoding Nalp1 so as to further study the role of this protein in innate immune defense and autoimmunity.
Sjogren's Syndrome As A Disorder Of Anti-receptor Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$211,527.00
Summary
A new approach to understanding Sjogren's syndrome Sjogren's syndrome (SS) is a frequent cause of illness predominantly in women, leading to frequent attendances to medical, dental and allied health practitioners. Historically considered a rarity, SS, in both its primary and secondary forms, is arguably the commonest manifestation of human systemic autoimmunity. Increasingly recognised by clinicians as the unifying diagnosis underlying a plethora of chronic disabling symptoms in women from the f ....A new approach to understanding Sjogren's syndrome Sjogren's syndrome (SS) is a frequent cause of illness predominantly in women, leading to frequent attendances to medical, dental and allied health practitioners. Historically considered a rarity, SS, in both its primary and secondary forms, is arguably the commonest manifestation of human systemic autoimmunity. Increasingly recognised by clinicians as the unifying diagnosis underlying a plethora of chronic disabling symptoms in women from the fourth decade and beyond, therapeutic options remain limited due to our primitive understanding of its cause. Emerging evidence suggests that rather than a consequence of physical destruction of salivary and tear glands by cells of the immune system, severe dryness of the mouth and eyes in SS might be caused by antibodies which block the transmission of signals from tiny nerves to receptors in these glands. We also have evidence that other symptoms experienced by patients with SS, including abnormal sweating, irritable bladder and bowel, and Raynaud's phenomenon, may also be the consequence of blockage of nerve supply. Furthermore, we have detected these blocking antibodies in patients with both primary SS and rheumatoid arthritis accompanied by secondary SS, pointing for the first time to a common underlying cause for SS in these two settings. We propose a new approach to understanding Sjogren's syndrome, as a disease of anti-receptor autoimmunity, akin to Graves disease of the thyroid gland. This opens up exciting possibilities for the development of new techniques for the diagnosis and treatment of SS.Read moreRead less
Cell-mediated Immune Responses In Cytomegalovirus-induced Myocarditis
Funder
National Health and Medical Research Council
Funding Amount
$238,407.00
Summary
The proposed research will provide a clearer understanding of the body's immune response to virus and self tissues in inflammatory heart disease. Inflammation of the heart, myocarditis, can occur following virus infection. The condition may be chronic and persist for a long time even after the virus infection has resolved. The autoimmune response attacks the body's own tissues and involves reactivity to a heart protein, namely myosin. Important immune cells (B and T cells) play a role in the dis ....The proposed research will provide a clearer understanding of the body's immune response to virus and self tissues in inflammatory heart disease. Inflammation of the heart, myocarditis, can occur following virus infection. The condition may be chronic and persist for a long time even after the virus infection has resolved. The autoimmune response attacks the body's own tissues and involves reactivity to a heart protein, namely myosin. Important immune cells (B and T cells) play a role in the disease process. Antibodies are produced by B cells during the virus infection which react to myosin but we do not know the reactivity of T cells in this disease. Natural molecules (cytokines) produced by our body are important for shaping our immune response (T and B cell-mediated) in virus infections and diseases. Autoimmune disease is a result of a mistake by our immune system. Such diseases can be triggered by virus infection and require immunotherapy for correction. In the project, we propose to : 1. Investigate immunological responses of immune cells (T cells) in the heart using an experimental mouse model of cardiovascular disease. 2. Examine the response of T cells to myosin using the mouse model of infection with a herpesvirus, cytomegalovirus (CMV). 3. Study the role of cytokines and immunotherapy in our CMV-triggered myocarditis model. Determination of the events leading to cardiovascular disease will allow developments of improved treatment and potential vaccinations against inflammatory heart disease. The findings from the proposed project are expected to have broader impact for other viruses invading the heart and their associated diseases in man.Read moreRead less
Role Of The IFN-induced Helicase IFIH1 In Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$630,621.00
Summary
Type 1 diabetes (T1D) is presently the most common chronic disease of childhood and is increasing, with incidence in children under five doubling over the last five years. Recent findings indicate the ifih1 gene is important in T1D. Our research aims to establish the contribution of this gene to the disease. It is hoped that recognition of relevant pathological molecules will allow identification of risk factors for disease development and, ultimately, targets for therapeutic intervention.
A Functional Genomic Approach To The Genetics Of Autoimmune (type A) Gastritis
Funder
National Health and Medical Research Council
Funding Amount
$467,640.00
Summary
The thymus produces white blood cells which defend the body from infections and cancer. Unfortunately, these white blood cells can also cause disease if they target the body's own tissues. These disesaes are called autoimmune diseases, and an example of such a disease is autoimmune (type A) gastritis, in which the white cells target the acid-producing cells of the stomach. The resulting damage can lead to the development of pernicious anaemia (vitamin B12 deficiency) and cancer of the stomach. T ....The thymus produces white blood cells which defend the body from infections and cancer. Unfortunately, these white blood cells can also cause disease if they target the body's own tissues. These disesaes are called autoimmune diseases, and an example of such a disease is autoimmune (type A) gastritis, in which the white cells target the acid-producing cells of the stomach. The resulting damage can lead to the development of pernicious anaemia (vitamin B12 deficiency) and cancer of the stomach. This project studies a mouse model of autoimmune gastritis with the aim of identifying the genes that encode susceptibility to the disease in this model. Ultimately, this information should help us to devise therapies that can be applied to the clinical situation. We have previously identified the locations of the genes which are responsible for causing gastritis in these mice. Two of them are very close together on one chromosome and appear to be very important because they have the strongest effects. Furthermore, there is some evidence that these genes may also be involved in determining susceptibility to diabetes and lupus. This project aims to further characterise these genes by locating them more exactly and by examining their effect on mice not normally prone to gastritis.Read moreRead less
The Role Of Post-translationally Modified Antigen In Rheumatoid Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$609,535.00
Summary
Rheumatoid arthritis (RA) is an inflammatory disease of joints. People who get RA often develop antibodies which react against proteins found in inflamed joints. We will investigate why cells of the immune system react against these proteins in RA, and identify which joint proteins, especially abnormal proteins, are targeted. This will allow us to design new approaches to treat RA in a way that just targets the response to these abnormal proteins, rather than the entire immune system.