Phenotypes, Interactions, and Functions of Cells of the Adaptive Immune System in the Healing Heart (A06 (P06))

• Subject Area: Cardiology, Angiology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 422681845

Based on our hypothesis that antigen-specific CD4+ T cells orchestrate post-infarct lesion remodelling, we will explore the consequences of antigen recognition in a mouse model of myocardial infarction with several pharmacological approaches, including disruption of the interaction between the major histocompatibility complex and T-cell receptors, and by boosting protective immunity with mRNA-guided expression of interleukin 2 that will expand immunosuppressive T-regulatory cells. We will interrelate this with autoimmunity data from patients in a prospective exploratory clinical trial (PHENO-HEART MI; >500 participants planned), which will combine follow-up after myocardial infarction with deep immune phenotyping. We will screen for the major histocompatibility complex immunopeptidome in humans and assess the functionality of human immune cells using a mouse model of immune-humanised non-obese diabetes/ severe combined immunodeficiency that will be subjected to experimental myocardial infarction. Our work thus aims to identify the functional and clinical relevance of human myocardial infarction-specific CD4+ T cells, and to guide the future development of clinical therapies that involve immunomodulation or vaccination against auto-antigens to improve post-myocardial infarction cardiac health.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1425: Heterocellular Nature of Cardiac Lesions: Identities, Interactions, Implications
• Applicant Institution: Albert-Ludwigs-Universität Freiburg
• Project Head: Professor Dr. Dennis Wolf