The Role Of Perivascular Macrophages In The Regulation Of Skin Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$616,518.00
Summary
Neutrophils are key defenders against bacterial infections. In this application we will test the hypothesis that perivascular macrophages play a critical role in the recruitment of neutrophils to site of cutaneous infection, and that these cells are targeted and destroyed by bacterial virulence factors. Our studies will gain novel insight into the leukocyte homing paradigm and shed new light on the mechanisms of microbial immuno-evasion.
Mast cells (MC) are key regulators of chronic skin inflammation, such as atopic eczema, and can also give rise to a group of diseases called mastocytosis. How MC numbers are regulated in these conditions is poorly understood. We have identified a novel circulating precursor cell that gives rise to MC. We will determine the function of these precursors in skin diseases, including eczema and mastocytosis, with the aim to curtail the course of of these difficult-to-treat conditions.
Determination Of An Action Spectrum For Ultraviolet Radiation-induced Immunosuppression In Humans
Funder
National Health and Medical Research Council
Funding Amount
$213,500.00
Summary
Ultraviolet (UV) radiation causes mutations in the skin which can develop into cancers many years later. The skin's immune system is an important defence that prevents most potentially cancerous cells from developing into skin tumours. UV also suppresses skin immunity, allowing cancer cells to proliferate unchecked. There is also evidence that this UV-induced immunosuppression may have important effects on infectious diseases such as herpes virus, leprosy and tropical ulcers. Sunlight contains U ....Ultraviolet (UV) radiation causes mutations in the skin which can develop into cancers many years later. The skin's immune system is an important defence that prevents most potentially cancerous cells from developing into skin tumours. UV also suppresses skin immunity, allowing cancer cells to proliferate unchecked. There is also evidence that this UV-induced immunosuppression may have important effects on infectious diseases such as herpes virus, leprosy and tropical ulcers. Sunlight contains UVB, which causes sunburn, and UVA. Until recently, UVA was thought to have little effect on skin immunity. We have previously shown that both broadband UVB and UVA are immunosuppressive, even after single exposures equivalent to 8 minutes of sunlight. It is not known which UVA wavelengths are most immunosuppressive. These studies will use a xenon arc solar simulator and a series of interference filters to produce narrow UVB and UVA wavebands. The effects of these wavebands on humans can be studied by deliberately eliciting immune responses to substances which volunteers are already sensitive to. One model of skin immunity in these studies is allergy to nickel (in earrings and costume jewellery), which affects 10% of women. The volunteers' backs are exposed to different UV wavelengths, and then nickel patches are taped to both the UV-exposed areas and adjacent, unexposed areas. By comparing the intensity (redness and thickness) of these nickel reactions, immunosuppression caused by each waveband can be measured. Similarly, the Mantoux reaction (in people vaccinated against tuberculosis) provides another, complementary model of skin immunity. Knowledge of the immune effects of different UV wavelengths (an action spectrum for UV immunosuppression) would improve understanding of skin cancer and enable development of better sunscreens, which currently offer only partial immune protection.Read moreRead less
Immune Privilege Of The Hair Follicle: Implications For Alopecia Areata
Funder
National Health and Medical Research Council
Summary
The skin, the second largest organ in the body after the skeleton, is of primary importance to the survival of mammalian life. Hair follicles are complex skin appendages, problems of which have an impact on human health and emotional welfare disproportionate to their small dimensions. In this study we will investigate the role of the immune system in the hair loss disease, alopecia areata, one of the most common human autoimmune diseases with the aim of finding more effective avenues of treatmen ....The skin, the second largest organ in the body after the skeleton, is of primary importance to the survival of mammalian life. Hair follicles are complex skin appendages, problems of which have an impact on human health and emotional welfare disproportionate to their small dimensions. In this study we will investigate the role of the immune system in the hair loss disease, alopecia areata, one of the most common human autoimmune diseases with the aim of finding more effective avenues of treatment for this poorly understood disease.Read moreRead less
Targeted Redox Therapy For Photoageing Prevention And Treatment
Funder
National Health and Medical Research Council
Funding Amount
$562,815.00
Summary
Our goal is to target natural reduction/oxidation (redox) modifiers, i.e. niacin and sulforaphane, to the skin deeper layers to treat photoageing. Both drugs have been separately shown to prevent UV induced skin cancer. The outcomes of this project will be safer and more effective prevention and treatment of sun damaged skin. This project can provide health benefits to Australians from improved treatment of sun damage, and economic benefits to the nation.
Dynamics And Mechanisms Of Neutrophil Migration During Tissue Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$529,577.00
Summary
Neutrophil granulocytes are central mediators of inflammatory conditions and infections. It is currently unclear how neutrophils navigate through inflamed tissues and how they detect damaged cells and/or pathogens. This proposal will use cutting-edge multi-photon microscopy to dissect the dynamics and mechanisms of neutrophil behaviour in real time in living animals. These experiments will provide a new understanding of the development of inflammatory diseases.
Characterisation Of Autoreactive T Cells In Chronic Idiopathic Urticaria Would Improve Its Diagnosis And Treatment.
Funder
National Health and Medical Research Council
Funding Amount
$97,182.00
Summary
Chronic idiopathic urticaria (CIU) is a disease in which itchy hives recur due to no apparent trigger. It is an autoimmune disease in which the immune system reacts against certain cells in the skin, called mast cells and basophils. It is unclear how this occurs. Once activated, mast cells and basophils release a chemical called histamine, which is responsible for the rash. I aim to identify the immune reactions that occur in CIU, develop reliable tests for diagnosis and improve treatment of CIU ....Chronic idiopathic urticaria (CIU) is a disease in which itchy hives recur due to no apparent trigger. It is an autoimmune disease in which the immune system reacts against certain cells in the skin, called mast cells and basophils. It is unclear how this occurs. Once activated, mast cells and basophils release a chemical called histamine, which is responsible for the rash. I aim to identify the immune reactions that occur in CIU, develop reliable tests for diagnosis and improve treatment of CIU.Read moreRead less
Specific Targeting Of Nanosystems By Cutaneous Delivery
Funder
National Health and Medical Research Council
Funding Amount
$985,026.00
Summary
Substances have long been applied to the skin for therapeutic or cosmetic purposes, but the range of suitable compounds is limited. Consequently, there is a need for a wider range of compounds which can be delivered effectively into the skin for targeted treatment, diagnostic imaging and vaccination. New nanomaterial drug delivery systems are being increasingly used for these purposes. We seek to understand the properties of nanosystems that will enable improved drug targeting via the skin.
To Describe The Regional Differences In The Innate Immune System Of The Skin Using Intra-vital Multiphoton Microscopy And Understand Its Functional Consequences In A Cutaneous Parasite Infection Model.
Funder
National Health and Medical Research Council
Funding Amount
$97,182.00
Summary
This study is the first of its kind to map the innate immune system, the body's first line of defence, in the skin - coined the "immune atlas". Researchers have shown regional differences in innate immune cells which could explain how infections develop at different sites of the body. Although they have shown this in a cutaneous leishmaniasis model, a parasite endemic in most parts of the world, it may have implications also for inflammatory skin conditions such as eczema or psoriasis.