1. Phospholipid oxidation generates potent anti-inflammatory lipid mediators that mimic structurally related pro-resolving eicosanoids by activating Nrf2.

    Embo Molecular Medicine 7(5):593 (2015) PMID 25770125 PMCID PMC4492819

    Exposure of biological membranes to reactive oxygen species creates a complex mixture of distinct oxidized phospholipid (OxPL) species, which contribute to the development of chronic inflammatory diseases and metabolic disorders. While the ability of OxPL to modulate biological processes is incr...
  2. T cell lipid peroxidation induces ferroptosis and prevents immunity to infection.

    Journal of Experimental Medicine 212(4):555 (2015) PMID 25824823 PMCID PMC4387287

    The selenoenzyme glutathione peroxidase 4 (Gpx4) is a major scavenger of phospholipid hydroperoxides. Although Gpx4 represents a key component of the reactive oxygen species-scavenging network, its relevance in the immune system is yet to be defined. Here, we investigated the importance of Gpx4 ...
  3. Discovery of a Highly Potent Anti-inflammatory Epoxyisoprostane-Derived Lactone.

    Journal of the American Chemical Society 136(50):17382 (2014) PMID 25474746

    Epoxyisoprostanes EI (1) and EC (2) are effective inhibitors of the secretion of proinflammatory cytokines IL-6 and IL-12. In detailed studies toward the investigation of the molecular mode of action of these structures, a highly potent lactone (3) derived from 1 was identified. The known isopro...
  4. Discovery of a highly potent anti-inflammatory epoxyisoprostane-derived lactone.

    Journal of the American Chemical Society 136(50):17382 (2014) PMID 25474746

    Epoxyisoprostanes EI (1) and EC (2) are effective inhibitors of the secretion of proinflammatory cytokines IL-6 and IL-12. In detailed studies toward the investigation of the molecular mode of action of these structures, a highly potent lactone (3) derived from 1 was identified. The known isopro...
  5. Discovery of a Highly Potent Anti-inflammatory Epoxyisoprostane-Derived Lactone.

    Journal of the American Chemical Society 136(50):17382 (2014) PMID 25474746

    Epoxyisoprostanes EI (1) and EC (2) are effective inhibitors of the secretion of proinflammatory cytokines IL-6 and IL-12. In detailed studies toward the investigation of the molecular mode of action of these structures, a highly potent lactone (3) derived from 1 was identified. The known isopro...
  6. Fatty acid-induced mitochondrial uncoupling elicits inflammasome-independent IL-1α and sterile vascular inflammation in atherosclerosis.

    Nature Immunology 14(10):1045 (2013) PMID 23995233

    Chronic inflammation is a fundamental aspect of metabolic disorders such as obesity, diabetes and cardiovascular disease. Cholesterol crystals are metabolic signals that trigger sterile inflammation in atherosclerosis, presumably by activating inflammasomes for IL-1β production. We found here th...
  7. Fatty acid-induced mitochondrial uncoupling elicits inflammasome-independent IL-1α and sterile vascular inflammation in atherosclerosis.

    Nature Immunology 14(10):1045 (2013) PMID 23995233

    Chronic inflammation is a fundamental aspect of metabolic disorders such as obesity, diabetes and cardiovascular disease. Cholesterol crystals are metabolic signals that trigger sterile inflammation in atherosclerosis, presumably by activating inflammasomes for IL-1β production. We found here th...
  8. Transport and uptake of immunogenic lipids.

    Molecular Immunology 55(2):179 (2013) PMID 23174352 PMCID PMC3612381

    An increasing number of lipid mediators have been identified as key modulators of immunity. Among these is a family of glycolipids capable of cellular uptake, loading onto the MHC-like molecule CD1d and stimulation of NKT cells. NKT cells are particularly interesting because they bridge innate a...
  9. Transport and uptake of immunogenic lipids

    Molecular Immunology 55(2):179 (2013)

    Highlights ► We have explored the serum transport of glycolipids. ► Glycolipids transport is influenced by their chemical composition. ► Chemistry also influences cellular uptake. ► Therapeutic applications of glycolipids will depend heavily on lipid homeostasis. ► Lipid biol...
  10. Transport and uptake of immunogenic lipids

    Molecular Immunology 55(2):179 (2013) PMID 23174352 PMCID PMC3612381

    Highlights ► We have explored the serum transport of glycolipids. ► Glycolipids transport is influenced by their chemical composition. ► Chemistry also influences cellular uptake. ► Therapeutic applications of glycolipids will depend heavily on lipid homeostasis. ► Lipid biol...
  11. Synthesis of epoxyisoprostanes: effects in reducing secretion of pro-inflammatory cytokines IL-6 and IL-12.

    Angewandte Chemie. International edition in Eng... 52(20):5382 (2013) PMID 23592365

  12. Synthesis of epoxyisoprostanes: effects in reducing secretion of pro-inflammatory cytokines IL-6 and IL-12.

    Angewandte Chemie. International edition in Eng... 52(20):5382 (2013) PMID 23592365

  13. IL-21 restricts virus-driven Treg cell expansion in chronic LCMV infection.

    PLoS Pathogens 9(5):e1003362 (2013) PMID 23696736 PMCID PMC3656089

    Foxp3+ regulatory T (Treg) cells are essential for the maintenance of immune homeostasis and tolerance. During viral infections, Treg cells can limit the immunopathology resulting from excessive inflammation, yet potentially inhibit effective antiviral T cell responses and promote virus persiste...
  14. IL-21 restricts virus-driven Treg cell expansion in chronic LCMV infection.

    PLoS Pathogens 9(5):e1003362 (2013) PMID 23696736 PMCID PMC3656089

    Foxp3+ regulatory T (Treg) cells are essential for the maintenance of immune homeostasis and tolerance. During viral infections, Treg cells can limit the immunopathology resulting from excessive inflammation, yet potentially inhibit effective antiviral T cell responses and promote virus persiste...
  15. Scavenger receptors target glycolipids for natural killer T cell activation.

    Journal of Clinical Investigation 122(11):3943 (2012) PMID 23064364 PMCID PMC3484437

    NKT cells are innate-like T cells with powerful regulatory functions that are a promising target for immunotherapy. The efficacy of glycolipids, such as the prototypic NKT cell antagonist α-galactosylceramide (αGalCer), is currently being evaluated in clinical trials, but little is known about f...
  16. Scavenger receptors target glycolipids for natural killer T cell activation.

    Journal of Clinical Investigation 122(11):3943 (2012) PMID 23064364 PMCID PMC3484437

    NKT cells are innate-like T cells with powerful regulatory functions that are a promising target for immunotherapy. The efficacy of glycolipids, such as the prototypic NKT cell antagonist α-galactosylceramide (αGalCer), is currently being evaluated in clinical trials, but little is known about f...
  17. Nrf2 is essential for cholesterol crystal-induced inflammasome activation and exacerbation of atherosclerosis.

    European Journal of Immunology 41(7):2040 (2011) PMID 21484785

    Oxidative stress and inflammation--two components of the natural host response to injury--constitute important etiologic factors in atherogenesis. The pro-inflammatory cytokine interleukin (IL)-1 significantly enhances atherosclerosis, however, the molecular mechanisms of IL-1 induction within t...
  18. Nrf2 is essential for cholesterol crystal-induced inflammasome activation and exacerbation of atherosclerosis.

    European Journal of Immunology 41(7):2040 (2011) PMID 21484785

    Oxidative stress and inflammation--two components of the natural host response to injury--constitute important etiologic factors in atherogenesis. The pro-inflammatory cytokine interleukin (IL)-1 significantly enhances atherosclerosis, however, the molecular mechanisms of IL-1 induction within t...
  19. Fatty acid amide hydrolase shapes NKT cell responses by influencing the serum transport of lipid antigen in mice.

    Journal of Clinical Investigation 120(6):1873 (2010) PMID 20484813 PMCID PMC2877940

    The potent regulatory properties of NKT cells render this subset of lipid-specific T cells a promising target for immunotherapeutic interventions. The marine sponge glycolipid alpha-galactosylceramide (alphaGalCer) is the proto-typic NKT cell agonist, which elicits this function when bound to CD...
  20. Lysosomal recycling terminates CD1d-mediated presentation of short and polyunsaturated variants of the NKT cell lipid antigen alphaGalCer.

    PNAS 106(25):10254 (2009) PMID 19506241 PMCID PMC2693181

    Short or polyunsaturated lipid variants of the NKT cell antigen alpha-galactosylceramide (alphaGC) exhibit decreased potency and a Th2 bias in vivo despite conserved TCR contact residues and stable binding to CD1d at neutral and acidic pH. Using reagents to directly visualize lipids in their fre...