PMID- 26907999
OWN - NLM
STAT- MEDLINE
DCOM- 20161222
LR  - 20181113
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 6
DP  - 2016 Feb 24
TI  - Lipid peroxidation causes endosomal antigen release for cross-presentation.
PG  - 22064
LID - 10.1038/srep22064 [doi]
LID - 22064
AB  - 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.
FAU - Dingjan, Ilse
AU  - Dingjan I
AD  - Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, 
      Radboud University Medical Center, Nijmegen, 6525 GA, the Netherlands.
FAU - Verboogen, Danielle Rj
AU  - Verboogen DR
AD  - Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, 
      Radboud University Medical Center, Nijmegen, 6525 GA, the Netherlands.
FAU - Paardekooper, Laurent M
AU  - Paardekooper LM
AD  - Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, 
      Radboud University Medical Center, Nijmegen, 6525 GA, the Netherlands.
FAU - Revelo, Natalia H
AU  - Revelo NH
AD  - Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, 
      Radboud University Medical Center, Nijmegen, 6525 GA, the Netherlands.
FAU - Sittig, Simone P
AU  - Sittig SP
AD  - Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, 
      Radboud University Medical Center, Nijmegen, 6525 GA, the Netherlands.
FAU - Visser, Linda J
AU  - Visser LJ
AD  - Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, 
      Radboud University Medical Center, Nijmegen, 6525 GA, the Netherlands.
FAU - Mollard, Gabriele Fischer von
AU  - Mollard GF
AD  - Department of Chemistry, Bielefeld University, Bielefeld, 33501, Germany.
FAU - Henriet, Stefanie Sv
AU  - Henriet SS
AD  - Department of Pediatrics, Radboud University Medical Center, Nijmegen, 6525 GA, 
      the Netherlands.
FAU - Figdor, Carl G
AU  - Figdor CG
AD  - Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, 
      Radboud University Medical Center, Nijmegen, 6525 GA, the Netherlands.
FAU - Ter Beest, Martin
AU  - Ter Beest M
AD  - Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, 
      Radboud University Medical Center, Nijmegen, 6525 GA, the Netherlands.
FAU - van den Bogaart, Geert
AU  - van den Bogaart G
AD  - Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, 
      Radboud University Medical Center, Nijmegen, 6525 GA, the Netherlands.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160224
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Free Radical Scavengers)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Photosensitizing Agents)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 1.6.3.- (CYBB protein, human)
RN  - EC 1.6.3.- (NADPH Oxidase 2)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - H4N855PNZ1 (alpha-Tocopherol)
SB  - IM
MH  - Animals
MH  - Antigen Presentation
MH  - *Cross-Priming
MH  - Dendritic Cells/cytology/drug effects/*immunology
MH  - Endosomes/immunology/metabolism
MH  - Free Radical Scavengers/pharmacology
MH  - Gene Expression
MH  - Granulomatous Disease, Chronic/*immunology/metabolism/pathology
MH  - Histocompatibility Antigens Class I/genetics/immunology
MH  - Humans
MH  - Jurkat Cells
MH  - Lipid Peroxidation/drug effects/*immunology
MH  - Membrane Glycoproteins/genetics/*immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - NADPH Oxidase 2
MH  - NADPH Oxidases/genetics/*immunology
MH  - Photosensitizing Agents/pharmacology
MH  - Primary Cell Culture
MH  - Reactive Oxygen Species/antagonists & inhibitors/immunology/metabolism
MH  - T-Lymphocytes, Cytotoxic/cytology/drug effects/*immunology
MH  - alpha-Tocopherol/pharmacology
PMC - PMC4764948
EDAT- 2016/02/26 06:00
MHDA- 2016/12/23 06:00
PMCR- 2016/02/24
CRDT- 2016/02/25 06:00
PHST- 2015/07/09 00:00 [received]
PHST- 2016/02/05 00:00 [accepted]
PHST- 2016/02/25 06:00 [entrez]
PHST- 2016/02/26 06:00 [pubmed]
PHST- 2016/12/23 06:00 [medline]
PHST- 2016/02/24 00:00 [pmc-release]
AID - srep22064 [pii]
AID - 10.1038/srep22064 [doi]
PST - epublish
SO  - Sci Rep. 2016 Feb 24;6:22064. doi: 10.1038/srep22064.