The ‘Dyslipidemic insult’ – an inflammatory response to excess lipoproteins.

An excess of lipoproteins can result in their storage in inappropriate organs. This provokes the immune system and results in tissue damage and diseases, such as atherosclerosis and fatty liver.

We want to discover how these diseases are initiated and how germinal centre formation can influence plaque formation in the aorta.

We will look across multiple tissues to see how tissue identity imprints macrophage responses to dyslipidemia and how this can lead to inflammatory cross-talk between tissues.

A special case will be the bone marrow, where lipoproteins are thought to interact with clonal haematopoiesis, perhaps through modifying niche macrophages.

We outline how signalling through the Interleukin 7 receptor permits bone marrow B cells to take up lipoproteins to actually aid their growth, including in leukemia.To achieve this, we have created the first experimental system that allows a window into lipoprotein uptake and for monitoring the ‘Dyslipidemic insult’.

We provide extensive preliminary results and outline our novel mouse models.

Our approach uses multiple next-generation sequencing approaches together with classical pathology and immunology techniques.Our approach aims at disease prevention rather than cure, with an emphasis on atherosclerosis and fatty liver disease. We harness the power of immunotherapy to see if modifying immune responses can alleviate disease.