Kennedy Trust Prize Studentships
The role of immunity in cardiovascular disease
- Project No: Clinical-6
- Intake: 2024 KIR Clinical
The immune system is integral to the cardiovascular health and disease. Targeting inflammation ameliorates cardiovascular outcomes. Atherosclerosis, the underlying cause of cardiovascular disease, is conceptualised as a lipid-driven inflammation. Recent single cell atlases from human atherosclerotic lesions has identified that – contrary to traditional beliefs – T cells outnumber macrophages by 2:1. Several effector and tissue memory T cells subsets are identifiable alongside unconventional T cells. New tools have improved our ability to not only define distinct subsets of tissue-associated T cells, but also to address their functions in situ in human tissues. These T cell subsets include both “conventional” memory T cells, some with specific tissue-associated memory profiles, as well as unconventional T cell subsets such as MAIT cells. The latter are involved in a range of inflammatory and infectious diseases, as well as in tissue homeostasis. We can address in detail the phenotype and function of the T cell infiltrate, as well as the receptor specificity of the conventional and unconventional T cell populations.
Overall, this project aims to investigate the biology and regulation of vascular lymphocytes and how they function in health and disease. Applying single cell technologies and functional studies we will study the relevance and prevalence of lymphoid cells in human and experimental atherosclerosis. The results will contribute to our understanding of the role of vascular immune cells in cardiovascular health and disease and it will explore the fundamental molecular mechanisms regulating vascular tissue immune cell responses. It will also open the door to specifically target the cells of relevance to provide new approaches to treat and prevent cardiovascular disease.
KEYWORDS (5 WORDS)
Immunology, cardiovascular disease, atherosclerosis, lymphocytes, immunity.
The student will benefit from the availability of in-house state-of-the-art single cell technologies including transcriptomics and proteomics approaches using dissociative methods but also spatial methodologies including spatial transcriptomics and CyTOF Hyperion for tissue imaging in human and mouse models of atherogenesis.
KEY PUBLICATIONS (5 maximum)
Provine NM, Klenerman P. MAIT Cells in Health and Disease. Annu Rev Immunol. 2020 Apr 26;38:203-228. doi: 10.1146/annurev-immunol-080719-015428. Epub 2019 Jan 27.
Depuydt, M.A.C., Schaftenaar, F.H., Prange, K.H.M. et al. Single-cell T cell receptor sequencing of paired human atherosclerotic plaques and blood reveals autoimmune-like features of expanded effector T cells. Nat Cardiovasc Res 2, 112–125 (2023). https://doi.org/10.1038/s44161-022-00208-4
de Winther MPJ, Bäck M, Evans P, Gomez D, Goncalves I, Jørgensen HF, Koenen RR, Lutgens E, Norata GD, Osto E, Dib L, Simons M, Stellos K, Ylä-Herttuala S, Winkels H, Bochaton-Piallat ML, Monaco C. Translational opportunities of single-cell biology in atherosclerosis. Eur Heart J. 2022 Dec 7:ehac686. doi: 10.1093/eurheartj/ehac686. PMID: 36478058.
Dib, L., Koneva, L.A., Edsfeldt, A. et al. Lipid-associated macrophages transition to an inflammatory state in human atherosclerosis, increasing the risk of cerebrovascular complications. Nat Cardiovasc Res 2, 656–672 (2023). https://doi.org/10.1038/s44161-023-00295-x
Engelen SE, Robinson AJB, Zurke YX, Monaco C. Therapeutic strategies targeting inflammation and immunity in atherosclerosis: how to proceed? Nat Rev Cardiol. 2022 Jan 31:1-21. doi: 10.1038/s41569-021-00668-4. PMID: 35102320
THEMES (4 key themes)
Immunology, Cardiovascular Science
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