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Cellular And Molecular Pathways Regulating Airway Mucosal Dendritic Cells During Onset Of Allergic Airways Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$491,065.00
Summary
Allergic airways inflammation (AAI), which leads to debilitating disease such as allergic asthma, is a condition medaited by the abnormal activity of the immune system towards essentially harmless inhlaed allergens. Two special cell types of the immmune system that are important in controlloing the onset and persistence of AAI are known as dendritic cells (DC) and T helper type 2 cells (Th2 cells). DC are located in all parts of the respiratory tract and are important in providing control signal ....Allergic airways inflammation (AAI), which leads to debilitating disease such as allergic asthma, is a condition medaited by the abnormal activity of the immune system towards essentially harmless inhlaed allergens. Two special cell types of the immmune system that are important in controlloing the onset and persistence of AAI are known as dendritic cells (DC) and T helper type 2 cells (Th2 cells). DC are located in all parts of the respiratory tract and are important in providing control signals to Th2 cells to become switched on and start to react to an inhaled allergen. Th2 cells then generate a variety of signals that initiate an cascade of immune responses towards the allergen that ultimately can lead to AAI and asthma if left unchecked, however this process remians relatively poorly understood. This project aims to examine how DC and Th2 interact, and at what level DC activity can be regulated so that unchecked Th2 immunity to harmless inhaled allergens can be controlled. The hope is to be able to identify new cellular and molecular pathways that can eventually become the target for new generations of preventative and therapeutic drugs.Read moreRead less
Initiating Events In The Development Of Allergic Airway Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$452,545.00
Summary
Despite recent advances we still do not understand the basic mechanisms which underlie the development of allergic airway inflammatory diseases such as rhinitis and asthma. It has been previously shown that when pollen are exposed to water they release a large number of very small starch granules which contain a number of potent allergens as well as plant steroids. In addition house dust mite allergens which are strongly associated with asthma are mostly located in small faecal pellets. Both the ....Despite recent advances we still do not understand the basic mechanisms which underlie the development of allergic airway inflammatory diseases such as rhinitis and asthma. It has been previously shown that when pollen are exposed to water they release a large number of very small starch granules which contain a number of potent allergens as well as plant steroids. In addition house dust mite allergens which are strongly associated with asthma are mostly located in small faecal pellets. Both these particles are ideally sized to enter the respiratory tract and initiate inflammatory responses. We have shown that these responses appear to be of the type that is needed to initiate allergic reactions. We intend to further study the interactions of these small inhaled allergen containing particles with cells of the respiratory tract. In this proposal we will look at both alveolar macrophages and respiratory epithelial cells. These approaches will not only provide new information about the processes of airway inflammation caused by allergens but may also define new therapeutic approaches to the treatment of these diseases.Read moreRead less
THE INTERFACE BETWEEN INNATE AND ADAPTIVE IMMUNITY
Funder
National Health and Medical Research Council
Funding Amount
$4,905,420.00
Summary
Allergic disorders including asthma are amongst the most prevalent diseases in Australia afflicting up to 25% of the population and costing the Australian Government in excess of $600 million annually. This program aims to understand the molecular and cellular mechanisms controlling airway inflammation, focusing on the cross-talk between scavenger cells at airway surfaces and circulating cells of the immune system. These studies will combine sophisticated mouse models of airway inflammation in t ....Allergic disorders including asthma are amongst the most prevalent diseases in Australia afflicting up to 25% of the population and costing the Australian Government in excess of $600 million annually. This program aims to understand the molecular and cellular mechanisms controlling airway inflammation, focusing on the cross-talk between scavenger cells at airway surfaces and circulating cells of the immune system. These studies will combine sophisticated mouse models of airway inflammation in the laboratory with clinical investigation and analysis of human tissue. Understanding these processes will translate into better treatments for patients suffering from life-threatening allergy and asthma.Read moreRead less
Inhibition Of Allergic Airway Inflammation By Nanoparticles
Funder
National Health and Medical Research Council
Funding Amount
$540,075.00
Summary
Inhaled air pollution particulate matter causes asthma exacerbations, with 'ultrafine' nanoparticles thought to play a major role. Unexpectedly, we recently found that, by contrast, administration of inert ultrafine nanoparticles prevents allergic airway inflammation. We will identify the key particle physical and chemical properties associated with this novel type of disease inhibition, study particle effects in clinically-relevant disease models and identify mechanisms of action.
Developmental Aspects Of Respiratory Inflammation, Allergy And Asthma
Funder
National Health and Medical Research Council
Funding Amount
$7,169,609.00
Summary
Asthma develops as a complex series of interactions between genetic susceptibility and environmental exposures occurring in early life. While many children grow out of asthma others do not and develop the chronic form of the disease that persists into adult life. Our research involves understanding why some susceptible children develop asthma and why this becomes chronic in some. We will undertake studies in children to find out how and why this occurs. A major part of our studies involve longit ....Asthma develops as a complex series of interactions between genetic susceptibility and environmental exposures occurring in early life. While many children grow out of asthma others do not and develop the chronic form of the disease that persists into adult life. Our research involves understanding why some susceptible children develop asthma and why this becomes chronic in some. We will undertake studies in children to find out how and why this occurs. A major part of our studies involve longitudinal studies in cohorts of children recruited before birth. Having the ability to study children as they grow and develop conditions such as allergies and asthma allows us to understand why these conditions occur and allow us to predict which children are likely to develop them. Our research Program also has a solid focus on Translational Research, in which we will use the findings from our basic science studies to develop and test new methods of preventing and of treating asthma. These studies will include new methods for preventing the development of allergies, preventing the damage done to the lungs by severe viral respiratory infections in early life and better methods of treating established allergic asthma by improving immunotherapy techniques. By its very nature, primary prevention of disease in young children is controversial and raises some interesting questions. As part of this Program we intend to initiate consultation and debate in public, academic, regulatory and industry circles. An important role for our Program is shifting the current emphasis away from treatment of established disease towards preventing disease occurring. This is the best way to decrease the health, social and economic burden of chronic diseases such as asthma.Read moreRead less
Molecular Characterisation Of TRAIL-regulated Signal Transduction Pathways And Their Role In The Development, Persistence, And Exacerbation Of Allergic Airways Disease
Funder
National Health and Medical Research Council
Funding Amount
$637,035.00
Summary
Molecules that promote the development, persistence, and exacerbation of asthma are only poorly defined. We have discovered a novel signalling pathway that is activated in the airway wall during asthma. Blocking a molecule that activates this pathway ameliorated asthma in mice. We now want to identify all the important components of this pathway and therapeutically modulate them to prevent the development, persistence, and exacerbation of asthma.
Allergen-sensitzation And Environmental Exposures In Early Life Interact Synergistically To Alter Lung Growth
Funder
National Health and Medical Research Council
Funding Amount
$425,088.00
Summary
Asthma develops as the result of complex interactions between genetic susceptibilities and environmental exposures. Approximately 40% of 6-year-old children in Perth are sensitized to inhaled allergens, however, only half of these have asthma. Allergic sensitization per se is therefore insufficient for the development of persistent asthma. A second hit, associated with lung inflammation in early life, increases this risk several fold. This second hit could come from viral infection or from other ....Asthma develops as the result of complex interactions between genetic susceptibilities and environmental exposures. Approximately 40% of 6-year-old children in Perth are sensitized to inhaled allergens, however, only half of these have asthma. Allergic sensitization per se is therefore insufficient for the development of persistent asthma. A second hit, associated with lung inflammation in early life, increases this risk several fold. This second hit could come from viral infection or from other inflammatory stimuli such as exposure to cigarette smoke, air pollutants and vehicle exhaust emissions. The timing of this second hit may well be important, particularly if it is early while the lungs are still growing and developing. The aim of this project is to examine interactions between allergen sensitization and exposure to environmental hazards in early life using a mouse model of allergic inflammation. We will test the hypothesis that the combination of allergic sensitization and viral infections in early life alter lung growth, airway function and airway hyperresponsiveness, however, exposure to air pollutants can not provide the 'second hit required to induce persistent asthma. Determining the role viral infection and environmental pollution have early in life may provide us with a strategy for intervention that could prevent life-long changes in respiratory function and airway hyperresponsiveness.Read moreRead less
Human CD4+ T-cell Epitope-based Therapeutic For Peanut Allergy
Funder
National Health and Medical Research Council
Funding Amount
$403,121.00
Summary
Peanut allergy affects ~2% of the population and peanuts are the major cause of fatal food-induced anaphylaxis. Peanut allergy usually appears in infancy and persists indefinitely. At present, unlike grass pollen allergy, there is no preventative treatment. Using blood cells from peanut-allergic patients, we will identify the components of major peanut allergens to use in _allergy shots� to develop tolerance on peanut exposure without risking anaphylaxis.
The Significance Of Aeroallergens In Eosinophilic Esophagitis
Funder
National Health and Medical Research Council
Funding Amount
$117,331.00
Summary
Eosinophilic esophagitis is an allergic condition that causes difficulty swallowing food and chest discomfort.Current diagnostic methods are inaccurate, and treatments are not curative. This project aims to clarify the role of promising new diagnostic techniques and to delineate the significance of aeroallergens (e.g. pollens) with a view to improving the treatment of eosinophilc esophagitis in the future. It is possible that simply avoiding pollens or treating hayfever in the future may be all ....Eosinophilic esophagitis is an allergic condition that causes difficulty swallowing food and chest discomfort.Current diagnostic methods are inaccurate, and treatments are not curative. This project aims to clarify the role of promising new diagnostic techniques and to delineate the significance of aeroallergens (e.g. pollens) with a view to improving the treatment of eosinophilc esophagitis in the future. It is possible that simply avoiding pollens or treating hayfever in the future may be all that is required to manage this condition.Read moreRead less