Vaccination is one of the most efficient and cost-effective methods of promoting health. Immunization as a possible treatment for cancer is a recent concept. One of the limitations of current vaccine protocols is inefficient priming for cytotoxic T lymphocytes, which are important in the control of viral infections and tumours. Skin dendritic cells are potent antigen presenters to the immune system. However, the skin historically has been regarded as a barrier and has not been intensively studied as an organ of immunization.
Our laboratory is engaged in studies to optimize the use of the skin as an organ to alter systemic immune responses. In separate projects, we are studying the priming or activation of T cells involved in models of systemic lupus erythematosus and juvenile onset diabetes mellitus.
Treating diabetes by modulating cross presentation
Type 1 diabetes mellitus is an autoimmune disease in which insulin-producing cells (termed beta cells) in the pancreas are destroyed. We have determined that beta cell death in the pancreas allows beta cell antigens to be processed by specialized antigen presenting cells called dendritic cells. These dendritic cells can then activate diabetes-inducing cytotoxic T cells through a process termed cross-presentation. We are currently determining which additional factors are required for the detrimental cross-presentation of self-antigen and how this may be inhibited.
SLE, UV light and T cell priming in the skin
Systemic lupus erythematosus (SLE) is an autoimmune disorder that can have devastating consequences. Lupus often begins in the skin and can worsen with exposure to sunlight. Recent experimental data in mouse models suggests that the skin may be the organ where T cells are first activated in lupus. Recent data also suggest that cytotoxic T cells may be involved in the initiation of lupus autoimmunity. A better understanding of how the skin may initiate immune responses will shed light on the role of the skin in initiating and/or perpetuating disease activity in systemic lupus erythematosus.
Epicutaneous modulation of T cell function
Recent evidence suggests that proteins or peptides can be applied on intact skin to vaccinate and produce both an antibody and a T cell response. Epicutaneous immunization (that is, on intact skin) offers potential for the development of tumour and virus-specific vaccines. In addition, it may be more cost effective as well as easier to administer than current methods of immunization. We are studying the epicutaneous application of peptides and proteins and methods to enhance their delivery and immunogenicity. In addition to being an ideal organ for the initiation of immune responses, the skin can suppress immune responses. It is particularly effective in this regard after exposure to ultraviolet light. Consequently, we are also studying how the skin may be used to induce tolerance and thereby possibly treat autoimmune disease.Grants
CIHR Operating Grant – Project: “Using the skin to control inflammation” (2013-2017)Honours & Awards
Junior Scholar, Arthritis Society of Canada - 2000
Martin M Hoffman Award for Excellence in Research, University of British Columbia Department of Medicine - 2001Research Group Members
Yiquin Zhang, Research Assistant
Paulina Piesik, Graduate Student
Douglas Carlow, Research Associate