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A8.15 Enzymatic lipid oxidation by 12/15-lipoxygenase regulates maturation and function of dendritic cells
  1. Tobias Rothe1,2,
  2. Olga Oskolkova4,
  3. Alexander Steinkasserer3,
  4. Valery N Bochkov4,
  5. Georg Schett1,
  6. Elisabeth Zinser3,*,
  7. Gerhard Krönke1,2,*
  1. 1Department of Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany
  2. 2Nikolaus Fiebiger Center of Molecular Medicine, University Hospital Erlangen, University of Erlangen-Nuremberg, 91054 Erlangen, Germany
  3. 3Department of Immune Modulation at the Department of Dermatology, University Hospital Erlangen, D-91052 Erlangen, Germany
  4. 4Department of Vascular Biology and Thrombosis Research, Center for Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, Austria

Abstract

Background and Objectives Upon the encounter of pathogens, dendritic cells (DCs) undergo a process of maturation, which allows them to initiate and orchestrate T-cell-driven immune responses. To avoid random T-cell activation and autoimmunity, respectively, DC maturation has to be tightly controlled. Here we aimed to elucidate the role of 12/15-lipoxygenase (12/15-LO)-mediated enzymatic lipid oxidation during DC-activation/maturation and the fine-tuning of the consecutive T-cell response.

Materials and Methods To delineate the role of 12/15-LO in DCs, we analysed the phenotype of 12/15-/- bone marrow-derived DCs and performed the model of experimental autoimmune enzephalomyelitis (EAE) in wild type and 12/15-LO-/- mice.

Results Differentiated bone marrow-derived DCs expressed 12/15-LO and were enriched in 12/15-LO-specific lipid oxidation products. Deletion of this enzyme resulted in enhanced DC maturation and a shift in their cytokine expression profile, which favoured the differentiation of Th17 T-cells. In contrast, both the activation of DCs and the development of Th17 T-cells were attenuated by exposure to 12/15-LO-derived oxidised phospholipids. The analysis of the lymphatic tissues of 12/15-LO-deficient mice confirmed an enhanced maturation of CD11c+CD11b+CD8- DCs as well as an increased differentiation of Th17 cells that was paralleled by an exacerbation of Th17-driven autoimmune disease.

Conclusions Our data identify 12/15-LO as novel factor modulating the function of DCs and indicate a central, and so far unrecognised, role for enzymatic lipid oxidation during the shaping of the adaptive immune response.

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