Atherosclerosis Immunity, Cardiovascular Neuroimmunology (Habenicht) 2

Project description

Our group recently reported that atherosclerosis is directly connected to the peripheral nervous system and the brain (Mohanta et al. 2022, Nature). It came to our attention several years ago that the peripheral nervous system uses the adventitia as their major conduit to reach all tissues. Following this line of reasoning, we now obtained proof-of-principle evidence that the nervous system can sense and possibly affect atherosclerosis via proxy actors, i.e. immune cell aggregates in the adventitia. We recently identified and functionally delineated interactions between nerves in the adventitia, artery tertiary lymphoid organs (ATLOs) and arteries that we termed neuroimmune cardiovascular interfaces (NICIs) (Mohanta et al. Nature 2022; Mohanta et al. 2014, Circulation Research; Mohanta et al. 2022, Circulation Research invited review, in preparation). These observations fill an unexpected important gap in our understanding of the pathogenesis of atherosclerosis. Indeed, NICIs define a new pathogenic principle of atherogenesis, because they initiate and ultimately form a structural artery-brain circuit (ABC) which controls atherosclerosis progression. Here, we intend to identify the mechanisms of crosstalk between the vascular system, the immune system and the PNS and also plan to use intervention strategies to target neurons in the PNS and the brain of experimental mice to impact atherosclerosis progression. In a multidisciplinary internationally organized project, we plan to define the structural and functional underpinnings of NICIs in the PNS of mice and humans using viral tracing, tissue clearing, 2-photon-microscopy, single cell transcriptome analyses among others. The ultimate goal of the project is to develop unprecedented therapeutic approaches to treat the root cuases of atherosclerosis. The scholarship recipient will have access to a graduate student program focusing on cardiovascular disease.