Lipid peroxidation causes endosomal antigen release for cross-presentation

Dingjan I, Verboogen DRJ, Paardekooper LM, Revelo NH, Sittig SP, Visser LJ, Fischer von Mollard G, Henriet SSV, Figdor CG, ter Beest M, van den Bogaart G (2016)
SCIENTIFIC REPORTS 6: 22064.

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Abstract
Dendritic cells (DCs) present foreign antigen in major histocompatibility complex (MHC) class I molecules to cytotoxic T cells in a process called cross-presentation. An important step in this process is the release of antigen from the lumen of endosomes into the cytosol, but the mechanism of this step is still unclear. In this study, we show that reactive oxygen species (ROS) produced by the NADPH-oxidase complex NOX2 cause lipid peroxidation, a membrane disrupting chain-reaction, which in turn results in antigen leakage from endosomes. Antigen leakage and cross-presentation were inhibited by blocking ROS production or scavenging radicals and induced when using a ROS-generating photosensitizer. Endosomal antigen release was impaired in DCs from chronic granulomatous disease (CGD) patients with dysfunctional NOX2. Thus, NOX2 induces antigen release from endosomes for cross-presentation by direct oxidation of endosomal lipids. This constitutes a new cellular function for ROS in regulating immune responses against pathogens and cancer.
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Dingjan I, Verboogen DRJ, Paardekooper LM, et al. Lipid peroxidation causes endosomal antigen release for cross-presentation. SCIENTIFIC REPORTS. 2016;6: 22064.
Dingjan, I., Verboogen, D. R. J., Paardekooper, L. M., Revelo, N. H., Sittig, S. P., Visser, L. J., Fischer von Mollard, G., et al. (2016). Lipid peroxidation causes endosomal antigen release for cross-presentation. SCIENTIFIC REPORTS, 6, 22064. doi:10.1038/srep22064
Dingjan, I., Verboogen, D. R. J., Paardekooper, L. M., Revelo, N. H., Sittig, S. P., Visser, L. J., Fischer von Mollard, G., Henriet, S. S. V., Figdor, C. G., ter Beest, M., et al. (2016). Lipid peroxidation causes endosomal antigen release for cross-presentation. SCIENTIFIC REPORTS 6:22064.
Dingjan, I., et al., 2016. Lipid peroxidation causes endosomal antigen release for cross-presentation. SCIENTIFIC REPORTS, 6: 22064.
I. Dingjan, et al., “Lipid peroxidation causes endosomal antigen release for cross-presentation”, SCIENTIFIC REPORTS, vol. 6, 2016, : 22064.
Dingjan, I., Verboogen, D.R.J., Paardekooper, L.M., Revelo, N.H., Sittig, S.P., Visser, L.J., Fischer von Mollard, G., Henriet, S.S.V., Figdor, C.G., ter Beest, M., van den Bogaart, G.: Lipid peroxidation causes endosomal antigen release for cross-presentation. SCIENTIFIC REPORTS. 6, : 22064 (2016).
Dingjan, Ilse, Verboogen, Danielle R. J., Paardekooper, Laurent M., Revelo, Natalia H., Sittig, Simone P., Visser, Linda J., Fischer von Mollard, Gabriele, Henriet, Stefanie S. V., Figdor, Carl G., ter Beest, Martin, and van den Bogaart, Geert. “Lipid peroxidation causes endosomal antigen release for cross-presentation”. SCIENTIFIC REPORTS 6 (2016): 22064.
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Data provided by Europe PubMed Central.

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Verboogen DRJ, González Mancha N, Ter Beest M, van den Bogaart G., Elife 6(), 2017
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VAMP8-mediated NOX2 recruitment to endosomes is necessary for antigen release.
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Sec61 blockade by mycolactone inhibits antigen cross-presentation independently of endosome-to-cytosol export.
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Paardekooper LM, van den Bogaart G, Kox M, Dingjan I, Neerincx AH, Bendix MB, Beest MT, Harren FJM, Risby T, Pickkers P, Marczin N, Cristescu SM., Sci Rep 7(1), 2017
PMID: 28761087
SWAP70 Organizes the Actin Cytoskeleton and Is Essential for Phagocytosis.
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