Theme 7: Atherosclerotic vascular disease: Role of the immune system

Atherosclerosis is an occlusive disease of arteries that causes heart attacks and strokes.  Together, they constitute the number 1 killer in our community.  While a high fat diet plays an important role, there is increasing recognition that inflammatory and immunological mechanisms play key contributing roles. 

Immunity: Our studies are directed towards a precise understanding of the role of the innate and adaptive immune system in the initiation and progression of atherosclerosis in the ApoE-/- mouse model of this disease. In particular, our studies are focused on the role of macrophages, NKT cells, NK cells, CD4 T cells, regulatory T cells, B cells and the interplay between these lymphocyte subsets in this process. We have compelling evidence for a key role of the cytokine, MIF (Macrophage Inhibitory Factor) and for NKT cells in the initiation of atherosclerosis. 

Significance: A precise understanding of the immunological processes leading to occlusive vascular disease can be expected to lead to novel treatment strategies to control atherosclerotic vascular disease that lead to heart attacks and strokes.

Working hypothesis:  Lipids enter the vessel wall and are taken by antigen presenting cells (APCs such as macrophages, dendritic cells and B cells.  These APCs present lipid antigen to NKT cells to initiate early lesions of atherosclerosis.  Secretion of TH1 cytokines by NKT cells recruit NK cells and CD4 T cells that may themselves be activated by protein antigens such as HSP60, leading to lesion progression.  Suppression by regulatory T cells is incomplete, contributing to lesion progression.

Students will be exposed to a unique intellectual environment that combines methods and expertise in Immunology and Inflammation at the Centre for Inflammatory Diseases, Department of Medicine, Southern Clinical School and in Vascular Biology at the Baker Heart Research Institute. Three PhD students are currently working on this project. 

Performance of past honours students: Two of our current 3 PhD students were the top students in their honours year, attaining the top student Nairn medal.