Glycolipid-sensing by Natural Killer T cells Group Freigang Natural killer T (NKT) cells are innate-like T cells with powerful immunoregulatory functions that recognize self and microbial glycolipids presented by CD1d molecules. While the efficacy of NKT cell agonists is currently explored in the immunotherapy of infectious diseases and cancer, the mechanisms that control CD1d antigen presentation and NKT cell activation in vivo still remain incompletely understood. This project characterizes pathways linking CD1d antigen presentation to lipid metabolism, and aims to define critical effector functions of NKT cells in microbial infections.
Molecular mechanisms of lipid-induced inflammation Group Freigang Cardiovascular diseases, particularly atherosclerosis-related diseases, remain the leading cause of death worldwide. While first clinical trials demonstrated the beneficial effects of anti-inflammatory therapies in CVD patients, a better understanding of the molecular mechanisms of vascular inflammation will be critical to develop more effective treatment strategies. Recent advances in the field of immunometabolism generated strong interest in delineating metabolic pathways that influence macrophage responses in atherosclerosis. In this project, we study mechanisms of IL-1–driven vascular inflammation that are linked to metabolic perturbation and mitochondrial dysfunction. En face preparations of the mouse aorta. The atherosclerotic lesions induced by feeding a high fat diet were revealed by staining with Oil Red O
Immune regulation by oxidized lipids Group Freigang Exposure of cellular membranes to reactive oxygen species creates a broad range of distinct oxidized phospholipid (OxPL) species that may actively modulate cellular signaling processes and immune responses. We have previously described cyclo-pentenone-containing OxPLs and their isoprostanes as pro-resolving lipid mediators. This project investigates the OxPL-signaling in myeloid cells during atherogenesis and microbial infection using functionalized lipid probes and a novel oxidative stress reporter. Cyclopentenone-containing oxidized phospholipids inhibit the production of the pro-inflammatory cytokine IL-6 by macrophages
