We are using high end imaging technologies, such as multi-photon microscopy, to dissect in real-time the working of the immune system in the skin. The Centenary Institute houses one of Australia’s leading imaging facilities to enable this research.
We study the pathogenesis of several inflammatory skin diseases such as psoriasis and atopic dermatitis. We are also investigating how we can manipulate the immune system for more infective strategies against melanoma and common skin infections, for example caused by “golden staph”.
“Golden staph” infections are a leading cause of infections in the hospital setting and account for more deaths in the industrialised world or HIV or tuberculosis infections.
Finding a Cure
Our research spans from bench to bedside. We have recently discovered a novel immune cell type in the skin – the dermal group 2 innate lymphoid cell (ILC2). We have found that these cells can cause inflammation in the skin of animals. We are now studying how these ILC2 cells are involved in eczema and atopic dermatitis formation in humans.
We have discovered using animal models that “golden staph” selectively destroys a specific immune cell type in the skin, the perivascular macrophage (PVM). This results in the dampening of the immune response against this dangerous pathogen. We are now investigating the function of PVM in human skin, and how we can improve their response in bacterial skin infections.
1) Cellular and molecular cues that regulate immune cell defense against infectious agents in the skin
The immune system is essential for our defence against infectious agents. Without an intact immune system, humans, like any other species, succumb quickly to the plethora of pathogens, including viruses, bacteria, and parasites, that continuously attempt to breach our protective barriers, for example the skin. This is best exemplified by conditions of immunodeficiency, such as genetic disorders of the immune system as well acquired immunodeficiency such as AIDS or immuno-suppressive therapy.
2) Mechanisms of type 2 skin inflammation
Our recent discovery of a novel skin resident immune cell population, namely dermal group 2 innate lymphoid cells (dILC2; Roediger et al, Nat Immunol, 2013), has sparked our interest in the pathogenesis of allergic skin disease, including atopic dermatitis. We are in the process of fully characterizing the function of these cells in normal mouse and human skin as well as in human skin diseases.
3) Kinetics and mechanisms of tumour defence by immune cells
Similarly to their function in the anti-microbial defence, the immune system, in particular cytotoxic effector T lymphocytes (CTL), is essential for recognising and destroying cancerous cells. Based on this notion, there is currently great hope to exploit the immune system in anti-cancer therapy. However, little is known about the dynamics and anatomical context of tumour cell destruction by CTL in vivo. We have developed a tumour model in combination with intravital multi-photon imaging to determine how CTL find and destroy target cells.
4) To develop targeted therapies against melanoma
Although recent years have seen dramatic improvement in the therapy of metastatic melanoma, disease often recurs within a short period time. Over the past years, we have invested significant effort in trying to understand the biology of melanoma.
5) Immunity beyond the skin
We are in the process of investigating how immune cells recognise pathogens, how they are destroyed, and how immune memory is generated. This has implications for the development of vaccines against these infections.
Professor Wolfgang Weninger, Head of Program
Phone: +61 2 9515 6861
Fax: +61 2 9565 6101
Professor and Head Immune Imaging Program
Raymond E. Purves Professor
Discipline of Dermatology
Sydney Medical School
Department of Dermatology
Royal Prince Alfred Hospital
Professor Weninger is a preeminent clinician scientist in the fields of dermatology and immunology. At the Centenary Institute, he leads the Immune Imaging Program. He is the Raymond E Purves Chair of Dermatology at the University of Sydney and heads the Department of Dermatology at Royal Prince Alfred Hospital, and also. Professor Weninger is a pioneer in the uncovering of immune cell behaviour during anti-pathogen and anti-tumour immune responses in the skin using intravital imaging technology. He is recognised for discovering several unique immune cell subsets and determining their function in the context of immune-mediated pathology. His ongoing work is aimed at understanding the mechanisms underlying skin allergies, and the pathways resulting in successful immunity against skin infections as well as melanoma.
Skin Imaging and Inflammation
The Skin Inflammation Group conducts primary research in multiple aspects of immunology, with a particular emphasis on using flow cytometry together with confocal and multiphoton microscopy to characterise immune cell behaviour in the skin during steady-state and following infection.