Rothe T, Gruber F, Uderhardt S, Ipseiz N, Rössner S, Oskolkova O, Blueml S, Leitinger N, Bicker W, Bochkov VN, Yamamoto M, Steinkasserer A, Schett G, Zinser E, Krönke G (2015)
Publication Type: Journal article
Publication year: 2015
Publisher: American Society for Clinical Investigation
Book Volume: 125
Pages Range: 1944-54
Journal Issue: 5
DOI: 10.1172/JCI78490
DCs are able to undergo rapid maturation, which subsequently allows them to initiate and orchestrate T cell-driven immune responses. DC maturation must be tightly controlled in order to avoid random T cell activation and development of autoimmunity. Here, we determined that 12/15-lipoxygenase-meditated (12/15-LO-mediated) enzymatic lipid oxidation regulates DC activation and fine-tunes consecutive T cell responses. Specifically, 12/15-LO activity determined the DC activation threshold via generation of phospholipid oxidation products that induced an antioxidative response dependent on the transcription factor NRF2. Deletion of the 12/15-LO-encoding gene or pharmacologic inhibition of 12/15-LO in murine or human DCs accelerated maturation and shifted the cytokine profile, thereby favoring the differentiation of Th17 cells. Exposure of 12/15-LO-deficient DCs to 12/15-LO-derived oxidized phospholipids attenuated both DC activation and the development of Th17 cells. Analysis of lymphatic tissues from 12/15-LO-deficient mice confirmed enhanced maturation of DCs as well as an increased differentiation of Th17 cells. Moreover, experimental autoimmune encephalomyelitis in mice lacking 12/15-LO resulted in an exacerbated Th17-driven autoimmune disease. Together, our data reveal that 12/15-LO controls maturation of DCs and implicate enzymatic lipid oxidation in shaping the adaptive immune response.
APA:
Rothe, T., Gruber, F., Uderhardt, S., Ipseiz, N., Rössner, S., Oskolkova, O.,... Krönke, G. (2015). 12/15-Lipoxygenase-mediated enzymatic lipid oxidation regulates DC maturation and function. Journal of Clinical Investigation, 125(5), 1944-54. https://doi.org/10.1172/JCI78490
MLA:
Rothe, Tobias, et al. "12/15-Lipoxygenase-mediated enzymatic lipid oxidation regulates DC maturation and function." Journal of Clinical Investigation 125.5 (2015): 1944-54.
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