Defining The Role Of Kidney CD103+Dendritic Cells For Treatment Of Chronic Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$599,431.00
Summary
Chronic kidney disease (CKD) is a major cause of death and morbidity. Current treatments for CKD are not effective and new therapeutic approaches are needed. Dendritic cells (DCs) are key immune cells and play a central role in kidney disease. We recently found that a major DC subset called CD103+ DCs harmed the kidney in an animal model of human CKD. This study is to determine how CD103+ DCs cause kidney damage, and how to target CD103+ DCs for development of new therapies for human CKD.
Dendritic Cells Govern The Balance Between Immunity And Homeostasis To Inhaled Antigen
Funder
National Health and Medical Research Council
Funding Amount
$816,131.00
Summary
The development of better intranasal vaccines hinges on the improved understanding of how the immune response is initiated following vaccine delivery into the upper airways. In this project we will provide fundamental understanding of how immune responses to inhaled antigens are regulated; this considerable conceptual advance will lay the foundation for which new intranasally delivered immunotherapies will ultimately emerge.
Investigation Of Dendritic Cell Activation And Function In A Murine Model Of Plasmodium And Schistosoma Co-infection
Funder
National Health and Medical Research Council
Funding Amount
$358,938.00
Summary
Malaria is responsible for over 2 million deaths annually, mainly in sub-Saharan Africa. Importantly, around 1 billion people in malaria endemic areas are infected with parasitic worms, thus malaria and worm co-infections frequently occur. This project will investigate how malaria and worm parasites interact to influence the immune response and clinical outcomes of each other in a mouse infection model. This will provide new strategies for the design of effective treatments in co-endemic areas.
Dendritic Cell-mediated Induction Of T Cell Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$654,725.00
Summary
Australia has some of the highest rates of immune-mediated diseases in the world. These diseases include autoimmune, allergic and inflammatory conditions. We will use a mouse model to study how dendritic cells can prevent the onset of these conditions by inactivating the immune cells that cause them. Our findings will aid in understanding why these diseases develop and how they may be prevented and treated.
The Mezzanine T Cell Response: Intervening At The Coal Face
Funder
National Health and Medical Research Council
Funding Amount
$765,585.00
Summary
In an initial immune response, specialised cells in lymph nodes tell T cells to multiply; the stimulated T cells depart and enter target tissue (e.g. lung in the case of flu). We describe a new response whereby the target tissue itself can tell T cells to multiply further. This response in target tissues reveals a new way of altering immune responses. This is especially important as in many diseases, the primary lymph node response has already occurred, so cannot be therapeutically intervened.
Respiratory Viral Infections As Triggers Of Acute Severe Asthma Exacerbations In Atopics: Mechanistic Studies In An Experimental Model
Funder
National Health and Medical Research Council
Funding Amount
$659,494.00
Summary
An important unresolved issue in asthma research is why almost all the children who present in hospital emergency with very severe asthma attacks are both allergic and virally infected. This project will seek to define how immune responses to viruses and aeroallergens interact to create very severe inflammation in the airways thus precipitating the severest type of asthma attacks. Understanding the underlying mechanisms will hopefully provide new clues towards better treatments.
Developmental Stages Of In Vivo And In Vitro-generated Dendritic Cell Subsets And Regulation Of T Cell Differentiation.
Funder
National Health and Medical Research Council
Funding Amount
$88,087.00
Summary
Dendritic cells (DC) represent a diverse family of white blood cells that form a sentinel network throughout the body involved in the detection and eradication of pathogens and cancer cells. DC can originate from different precursor cells in the bone marrow. It is therefore possible that different types of DC perform differing functions. For instance, DC not only initiate immune responses but are also able to silence them. However, the ability of DC to instruct and orchestrate the immune respons ....Dendritic cells (DC) represent a diverse family of white blood cells that form a sentinel network throughout the body involved in the detection and eradication of pathogens and cancer cells. DC can originate from different precursor cells in the bone marrow. It is therefore possible that different types of DC perform differing functions. For instance, DC not only initiate immune responses but are also able to silence them. However, the ability of DC to instruct and orchestrate the immune response may not only depend upon their origins but also on where they encounter pathogens or cancer cells and what other signals are associated with this encounter. Due to their specialized capacity to instruct the immune response (e.g. T cells, B cells and NK cells) of impending danger, DC are used experimentally to more efficiently deliver vaccines to the immune response so as to eradicate cancer or infectious disease. However, in order to successfully use DC to deliver vaccines, one must first understand how these cells normally behave in the body and what signals can alter their functional ability to orchestrate immune responses. We can generate DC outside the body from their precursors. We can also isolate DC from the circulation. This project seeks to identify how various physiologic stimuli differentially regulate the functional behaviour of DC subsets and how this then influences the DC's ability to instruct the developing T cell immune response. Furthermore, whether these signals are the same for DC generated outside the body with those isolated from the blood. Of particular interest is whether differing types of DC and differing stages of their maturity will differentially influence the T cell's ability to secrete immune response hormones and to recognize and kill cancer cells. The findings of this study have direct implications of how to best harness DC to effectively deliver vaccines and generate potent immune responses against cancer and infectious disease.Read moreRead less
The Importance Of GM-CSF In Determining The Fate And Function Of Dendritic Cell (DC) Subsets: Resident DC, Inflammatory DC And Suppressive DC.
Funder
National Health and Medical Research Council
Funding Amount
$334,053.00
Summary
The hormone GM-CSF determines how infections are seen by the immune system GM-CSF is a hormone already in use for increasing the production of white blood cells. We have found that it also affects their function, especially that of specialised white blood cells that process infectious materials to be recognised by the immune system. This project aims to detail the effects of GM-CSF on specialised white blood cells.
The Structure And Composition Of The T-cell Receptor-CD3 Complex
Funder
National Health and Medical Research Council
Funding Amount
$434,644.00
Summary
Our research will provide a fundamental advance in our understanding of how foreign viruses and pathogens trigger the immune system. Gaining a greater understanding of these central events will facilitate the design of novel therapies to treat immune associated disorders such as transplant rejection, autoimmune disease and some cancers.
A New Approach To The Design And Evaluation Of T Cell Vaccines For Cancer And Infectious Disease.
Funder
National Health and Medical Research Council
Funding Amount
$394,137.00
Summary
Special white blood cells called dendritic cells teach the immune system to fight cancer and are a key component of therapeutic cancer vaccines. We identified a subtype of human dendritic cell that is predicted to be the most effective at mounting anti-cancer immune responses. We developed a novel antibody specific for these dendritic cells that can be used to deliver the vaccine directly to them and will use this to construct and validate a novel vaccine for cancer and viral infections.