atherosclerosis; inflammation; lipids; interleukin-1; metabolism
Keller Christian W, Freigang Stefan, Lünemann Jan D (2017), Reciprocal Crosstalk between Dendritic Cells and Natural Killer T Cells: Mechanisms and Therapeutic Potential, in Frontiers in Immunology
Keller CW, Loi M, Ewert S, Quast I, Theiler R, Gannagé M, Münz C, De Libero G, Lünemann JD, Freigang S (2017), The autophagy machinery restrains iNKT cell activation through CD1D1 internalization, in Autophagy
, 13(6), 1-12.
Friedli Olivier, Freigang Stefan (2017), Cyclopentenone-containing oxidized phospholipids and their isoprostanes as pro-resolving mediators of inflammation., in Biochim Biophys Acta
, 1862(4), 382-392.
Freigang Stefan (2016), The regulation of inflammation by oxidized phospholipids., in Eur J Immunol
, 46(8), 1818-1825.
Zysset Daniel, Weber Benjamin, Rihs Silvia, Brasseit Jennifer, Freigang Stefan, Riether Carsten, Banz Yara, Cerwenka Adelheid, Simillion Cedric, Marques-Vidal Pedro, Ochsenbein Adrian F, Saurer Leslie, Mueller Christoph (2016), TREM-1 links dyslipidemia to inflammation and lipid deposition in atherosclerosis, in Nature Communications
, 7, 13151.
Bretscher Peter, Egger Julian, Shamshiev Abdijapar, Trötzmüller Martin, Köfeler Harald, Carreira Erick M, Kopf Manfred, Freigang Stefan (2015), Phospholipid oxidation generates potent anti-inflammatory lipid mediators that mimic structurally related pro-resolving eicosanoids by activating Nrf2., in EMBO Molecular Medicine
, (5), 593-607.
Matsushita Mai, Freigang Stefan, Schneider Christoph, Conrad Marcus, Bornkamm Georg W, Kopf Manfred (2015), T cell lipid peroxidation induces ferroptosis and prevents immunity to infection., in J Exp Med
, 212(4), 555-568.
Egger Julian, Fischer Stefan, Bretscher Peter, Freigang Stefan, Kopf Manfred, Carreira Erik M (2015), Total Synthesis of Prostaglandin 15d-PGJ(2) and Investigation of its Effect on the Secretion of IL-6 and IL-12., in Org Lett
, 17(17), 4340-4343.
Cardiovascular diseases, in particular atherosclerosis, remain the leading cause of death worldwide; they also induce substantial morbidity and health care costs. Although dietary and pharmacological interventions are currently used to manage major risk factors, there is no effective treatment available that directly targets vascular inflammation. Metabolic dysfunction and chronic inflammation reciprocally interact in the pathogenesis of metabolic diseases, including atherosclerosis. Still, our understanding of the molecular mechanisms underlying this metabolic-immunological crosstalk remains very limited. We have recently characterized a novel pathway that selectively induces IL-1a-driven vascular inflammation and atherogenesis in response to metabolic perturbation. Our study identified fatty acid-induced respiratory uncoupling as the metabolic signal that triggers IL-1a secretion but simultaneously inhibits inflammasome activation and IL-1ß responses. These findings defined mitochondrial uncoupling as a previously unknown regulatory mechanism that relays metabolic stress to chronic inflammation. We therefore intent to investigate the role of physiological uncoupling in the regulation of IL-1 responses in atherosclerosis, metabolic dysfunction and microbial infection. We anticipate that these studies will not only extend our current understanding of a novel basic mechanism that links chronic inflammation and metabolic dysfunction, but will also identify new molecular targets that could be evaluated for the treatment of auto-inflammatory syndromes and metabolic disorders, such as obesity, diabetes and cardiovascular disease.