Genetic And Molecular Mechanisms Dysregulating CD4 T Cell Tolerance In Organ-specific Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$575,947.00
Summary
This project will analyse mechanisms that regulate CD4 T cells and normally prevent the immune system from attacking parts of our own body. Unknown errors in the control of T cells result in autoimmune diseases such as Type 1 diabetes, multiple sclerosis, Addison s disease and thyroid disease, where T cells damage or destroy vital organs. In order to develop rational, specific methods for treating and preventing these diseases, it is necessary to identify and understand the genetic and biochemic ....This project will analyse mechanisms that regulate CD4 T cells and normally prevent the immune system from attacking parts of our own body. Unknown errors in the control of T cells result in autoimmune diseases such as Type 1 diabetes, multiple sclerosis, Addison s disease and thyroid disease, where T cells damage or destroy vital organs. In order to develop rational, specific methods for treating and preventing these diseases, it is necessary to identify and understand the genetic and biochemical mechanisms that normally control T cell responses to self components, and how inherited defects lead these mechanisms to break down. The project focuses on defining how CD4 T cell regulation breaks down in a well established but poorly understood example of polygenic inherited susceptibility to autoimmune disease. Polygenic diseases are those where susceptibility is inherited in a complex way involving many different genes either acting together or in opposition, and the molecular basis for this kind of inheritance is particularly poorly understood. The project will analyse the basis for this kind of inheritance pattern by analysing the direct action of diabetes susceptibility genes at the level of the specific T cells responsible for autoimmune attack and in terms of the biochemical pathways within the T cells that are dysregulated. By identifying the mechanisms and biochemical pathways that are dysregulated in autoimmune disorders, the results of this project will concepts and targets for understanding and diagnosing autoimmune diseases and for developing new drugs or vaccines to prevent T cells damaging vital organs and cure these diseases.Read moreRead less
Targeting Antigen To Clec9A On Dendritic Cell For Humoral Immunity
Funder
National Health and Medical Research Council
Funding Amount
$744,624.00
Summary
Dendritic cells capture infectious organisms and display them to other immune cells to initiate immunity. The process of capturing organisms requires dendritic cells to express a variety of cell-surface receptors that detect components carried by infectious agents. Here we will examine the efficacy of attaching vaccine components to a targeting agent that binds one of these receptors with the aim of enabling dendritic cells to efficiently kick-start immunity against vaccine components.
Leptin As A Natural Regulator Of TFH Cell Differentiation And Vaccination Response
Funder
National Health and Medical Research Council
Funding Amount
$594,901.00
Summary
Follicular helper T (Tfh) cells constitute a CD4+ T cell subset that plays an instrumental role to support protective antibody responses in infection and vaccination. Although malnutrition is associated with poor vaccine responses and increased risks of infections, the mechanism is poorly understood. We will investigate the mechanism by which leptin, a hormone secreted by adipose cells, regulates Tfh cell function and vaccination response.
The Role Of Linked Cytokines In T Helper Cell Differentiation
Funder
National Health and Medical Research Council
Funding Amount
$390,504.00
Summary
An important class of T cells known as T Follicular Helper cells (TFH) orchestrate the immune response so that we can produce antibodies to fight infection. The novel finding that our Lab made last year is that the molecule interleukin 21 (IL-21) is a growth factor for TFH. The findings we have made thus far could be used in a number of ways. For eg, IL-21could be used to expand numbers of TFH, using them to boost vaccination or natural defences against viruses, bacteria and tumour cells.