Dissecting the regulation of T and B cell immune function via the resolvin D2-GPR18 axis in atherosclerosis

• Applicant: Professorin Dr. Sabine Steffens
• Subject Area: Cardiology, Angiology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 575688749

Cardiovascular disease is the leading global cause of death, with atherosclerosis—a chronic inflammation of arterial vessels—as the primary underlying pathology. Although recent progress has been made in developing anti-inflammatory therapies for coronary artery disease, challenges related to specificity and side effects remain, highlighting the need for novel therapeutic targets. Our research focuses on inflammatory lipid mediators and their receptors, including the endogenous ligand of the orphan G protein-coupled receptor GPR18, resolvin D2 (RvD2). Although GPR18 has been associated with protective functions in macrophages during atherosclerosis, transcriptomic data indicate its predominant expression in T and B lymphocytes. However, the function of the RvD2-GPR18 axis in these adaptive immune cells remains largely unknown. In preliminary work for this proposal, we confirmed the expression of GPR18 in the follicular zones of the spleen and in perivascular lymphoid clusters, indicating its importance for adaptive immunity. In addition, our preliminary results in Apoe-/-Gpr18-/- mice show increased plaque formation, altered splenic follicular structure and increased plasma IgM and IgG levels, suggesting that GPR18 acts as a negative switch of B and T cell activation in atherosclerosis. Based on these findings, our project aims to elucidate the role of GPR18 in adaptive immunity during atherosclerosis. To this end, we will (1) map GPR18 expression across immune cell subtypes in human and mouse atherosclerosis, (2) elucidate GPR18 signalling pathways in lymphocytes, and (3) characterize the effects of global and lymphocyte Gpr18 deficiency. With these studies, we hope to identify the lymphocytic RvD2-GPR18 signalling pathway as a promising therapeutic target for modulating adaptive immune responses in atherosclerosis.

• DFG Programme: Research Grants