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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.
Induction Of Antigen-specific Tolerance Through Inhibition Of RelB Function In Dendritic Cells
Funder
National Health and Medical Research Council
Funding Amount
$421,980.00
Summary
This proposal builds on preliminary data showing the possibility that responses of the immune system to antigens can be suppressed by modifying cells known as dendritic cells using an inhibitory drug. The drug appears to be able to control the ability of dendritic cells to educate the immune system about antigens. When antigens presented continuously are harmful to the immune system, they produce diseases such as rheumatoid arthritis and allergies. The experiments to be undertaken specifically l ....This proposal builds on preliminary data showing the possibility that responses of the immune system to antigens can be suppressed by modifying cells known as dendritic cells using an inhibitory drug. The drug appears to be able to control the ability of dendritic cells to educate the immune system about antigens. When antigens presented continuously are harmful to the immune system, they produce diseases such as rheumatoid arthritis and allergies. The experiments to be undertaken specifically look at means to prevent and reverse diseases like rheumatoid arthritis through the use of dendritic cells.Read moreRead less
The Immunological Microenvironment In The Synovium During Experimental Polyarthritis In The Rat
Funder
National Health and Medical Research Council
Funding Amount
$473,250.00
Summary
In this project, we aim to understand the process by which some forms of arthritis, as exemplified by rheumatoid arthritis (RA), cause inflammation and destruction of multiple joints. Such forms of arthritis are referred to collectively as polyarthritis. There is a strong evidence that RA has an immunological basis and that abnormal recognition of components of the joints by T lymphocytes orchestrates the inflammation that is characteristic of the disease. We believe that dispersal of disease-ca ....In this project, we aim to understand the process by which some forms of arthritis, as exemplified by rheumatoid arthritis (RA), cause inflammation and destruction of multiple joints. Such forms of arthritis are referred to collectively as polyarthritis. There is a strong evidence that RA has an immunological basis and that abnormal recognition of components of the joints by T lymphocytes orchestrates the inflammation that is characteristic of the disease. We believe that dispersal of disease-causing activated T lymphocytes in the blood accounts for the involvement of many joints. We have used a model of polyarthritis in rats to study the nature of the activated T lymphocytes, where they come from, how they are delivered to the blood stream and how they enter the joints. This project focuses on the crucial tissues that line the joints. We want to understand how the disease-causing activated T cells cause inflammation and how the immune system reacts to restrain them. We can undertake this work because we have developed three unique tools. Firstly, we can transfer arthritis with activated T lymphocytes and, therefore, study their behavior in an otherwise normal body. In this way, we can see how the body responds to the presence of disease causing cells. Secondly, we have introduced a genetic marker, which is essential if one wishes to distinguish the separate activities of the donor' and host cells. Thirdly, we can collect cells from the diseased paws, allowing us to examine their activities in vitro as well as in vivo. This model offers the opportunity to study the activities of the disease-causing cells and to identify points at which the disease cycle can be broken. It will allow us to design and-or test new treatments aimed at these points.Read moreRead less
Expression And Functions Of Leukocyte Immunoglobulin-like Receptor (LIR)-6 And LIR-4 In Inflammatory Arthritis (IA).
Funder
National Health and Medical Research Council
Funding Amount
$292,216.00
Summary
Rheumatoid arthritis (RA) that affects millions worldwide is characterised by uncontrolled activation of immune cells destroying ones own joints. The reasons for this excessive activation of cells are not known and existing treatments are limited to easing symptoms. We will study the role of new proteins named as Leucocyte Ig-like Receptors in regulating immune cell activation. Understanding mechanisms that control unwanted activation of immune cells is critical in preventing and treating RA.
Migration And Differentiation Of Dendritic Cells And Monocytes In Inflammatory Arthritis.
Funder
National Health and Medical Research Council
Funding Amount
$280,000.00
Summary
Dendritic cells and monocytes are of critical importance to the development and persistence of inflammatory disease in rheumatoid arthritis. Blocking this process at key strategic intervention points is a major focus of research to improve disease treatment. These studies examine the critical processes and molecules that control the entry of these cells to the joint in mice, and the derivation of cells that contribute directly to bone damage in the disease.
Investigating T Cell Tolerance And Organ-specific Auotimmunity Using Autoantigen Deficient Mice
Funder
National Health and Medical Research Council
Funding Amount
$441,000.00
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. Our studies will employ technologies to genetically manipulate mice to further our knowledge of this class of disease and to uncover the normal mechanisms that allow the immune system to prevent autoimmune attack. In particular we will gain information on the way that a new class ....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. Our studies will employ technologies to genetically manipulate mice to further our knowledge of this class of disease and to uncover the normal mechanisms that allow the immune system to prevent autoimmune attack. In particular we will gain information on the way that a new class of lymphocytes, known as regulatory lymphocytes, are able to protect against autoimmune disease. Such regulatory lymphocytes have been identified in humans and are attractive therapeutic agents to prevent a variety of immune-mediated diseases, including autoimmune diseases, allergy and transplantation rejection.Read moreRead less