The interplay of different immune cells determines the progression of atherosclerosis and the propensity to cause clinical symptoms, such as a myocardial infarction or stroke. Immune checkpoint regulators, including co-stimulatory and co-inhibitory molecules, are important modulators of immune responses in atherogenesis. 

• Co-stimulatory molecules in Atherosclerosis

Previously, we have unraveled how co-stimulatory CD40L-CD40, CD27-CD70 and GITR-GITRL interactions drive atherosclerosis. We found that the CD40L-CD40-TRAF6 axis is crucial in atherosclerosis, and we could develop small molecule inhibitors targeting CD40-TRAF6 interactions, termed TRAF-STOPs. TRAF-STOP treatment successfully blocked (established) atherosclerosis and is currently being tested and optimized for human administration. Using conditional knock-out mice for CD40 and CD40L, we found that CD40 on dendritic cells and macrophages as well as CD40L on T cells are crucial for atherogenesis. Moreover, we discovered that the co-stimulatory molecule CD27 is a critical mediator for regulatory T cell (Treg) survival, which led to attenuated inflammation and retards atherosclerosis. Our latest data show that GITR drives myeloid cell recruitment and activation in atherosclerosis, thereby inducing plaque growth and vulnerability.

• Amino acid metabolism in atherosclerosis
  

Currently we extended our studies to investigate how aberrant T cell regulation emanating from changes in T cell metabolism may be pro- or anti-atherogenic. Our latest study unraveled a novel mechanism by which the amino acid homoarginine reduces atherosclerosis, establishing that homoarginine modulates the T cell cytoskeleton and thereby mitigates T cell functions important during atherogenesis.