Immune modulation in atherosclerosis and vascular aneurysms
Atherosclerosis is a chronic inflammatory disease of the arterial wall responsible for most ischaemic cardiovascular diseases and stroke, the most frequent causes of death worldwide. Although not sharing all risk factors for atherosclerosis, abdominal aortic aneurysm (AAA) is also characterised by an inflammatory and destructive remodelling of the vessel wall and is responsible for a significant number of deaths in Western Countries. Both innate and adaptive immune responses have been involved in the initiation and progression of atherosclerosis and AAA. However, there is currently no specific therapeutic strategy targeting the immuno-inflammatory response in atherosclerosis and no medical therapy has been approved for the prevention of progression or rupture of AAA. Deciphering the role of specific subtypes of immune cells would lead to new, potent and specific therapeutic strategies to limit these devastating diseases.
We have recently shown that subpopulations of natural and/or inducible regulatory T (Treg) cells potently inhibit atherosclerotic lesion development and inflammation. We hypothesise that Treg cells and similarly, B cell type regulatory populations, have a broader role in the control of vascular inflammation and may significantly alter atherosclerosis or AAA development and progression. We will study in detail the mechanisms leading to recruitment of the different T and B cell subsets into the injured vessel wall and the pathways by which they modulate vascular inflammation. We will also develop novel immuno-modulatory and vaccination-based strategies to promote protective immune responses in atherosclerosis and AAA, with the aim to radically change the management and treatment of these common and serious vascular diseases.