Identification and characterization of the role of mucosal associated invariant T-cells in cardiovascular diseases

• Applicant: Dr. Tobias Radecke
• Subject Area: Cardiology, Angiology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 553892813

Cardiovascular diseases (CVDs) like myocardial infarction, stroke and acute limb ischemia are the leading cause of death worldwide. CVDs are mainly caused by atherosclerosis, a chronic low-grade inflammatory disease of the blood vessels, which is characterized by a complex immunological interaction of an innate and adaptive immune response. This knowledge was mainly based on experimental evidence until recently two clinical trials highlighted the beneficial effects of inflammation-targeted therapies. These studies provided direct proof of the concept that atherosclerosis is a chronic inflammatory disease for the first time. However, the precise mechanisms that control the development and progression of CVDs, including atherosclerosis, have not been fully elucidated yet. The role of inflammation seems to be even more complex as different immune responses seem to have contrary effects regarding the stages of atherosclerosis development. Mucosal-associated invariant T (MAIT) cells are innate-like T cells that interact between innate and adaptive immunity. These cells are capable of responding rapidly to a stimulus as innate cells, but on the other hand can expand and adapt to establish antigen memory as T cells, therefore making a bridge between innate and adaptive immunity. They are involved in pathologies associated with microbiota dysbiosis such as metabolic and liver diseases. Chronic inflammation and gut dysbiosis has been identified as an important contributor to the pathogenesis of CVDs, although the underlying mechanism needs to be further elucidated. In particular, the role of MAIT cells is completely unknown in this context. The aim of the current project is to investigate the role of MAIT cells in the regulation of vascular inflammation, remodeling and atherosclerosis development for the first time. We anticipate that our VORSCHAU NOCH NICHT GESENDET project will identify a new immune-regulatory player in atherosclerosis and might have important implications for targeting this cell type as a new therapeutic approach against atherosclerosis.

• DFG Programme: WBP Position