Monocyte – Treg interactions as key drivers of the cardiovascular remodelling after myocardial infarction (A1)

Both innate and adaptive immune responses control healing of the heart post-myocardial infarction. Previous studies could identify the recruitment of monocytes as well as regulatory T cells to the injured heart and show that both cell types critically participate to infarct wound healing. How these cells interact to execute their functions in the heart remains elusive.

Background

Monocytes dominate the cellular infiltrate in the first days after myocardial infarction, and participate to infarct wound healing. Importantly, monocyte differentiation and functional adaptation from specialization for cell debris removal towards supporting myocardial healing is driven by the local cytokine milieu. Whether regulatory T cells dictate monocyte differentiation and therefore the cardiac function after infarction is still unclear.

Rationale and aims

In this project we will elucidate how monocytes and Treg cell subsets regulate these processes and specifically focus on how myeloid and lymphoid populations communicate and interact in order to execute their concerted function.

Approach

We will complementarily use novel mouse models, high-end multi-colour fluorescence approaches such as light-sheet fluorescence microscopy and multicolour flow cytometry, and single-cell sequencing, to track and phenotype monocytes and their progeny as well as regulatory T cells, and investigate how these are influenced by type IL1-family and prototypical anti-inflammatory cytokines after myocardial infarction.