PMID- 33316542
OWN - NLM
STAT- MEDLINE
DCOM- 20220124
LR  - 20220124
IS  - 1878-3279 (Electronic)
IS  - 0171-2985 (Linking)
VI  - 226
IP  - 1
DP  - 2021 Jan
TI  - Cytotoxic activity of human dendritic cells induces RIPK1-dependent cell death.
PG  - 152032
LID - S0171-2985(20)30554-4 [pii]
LID - 10.1016/j.imbio.2020.152032 [doi]
AB  - Dendritic cells (DCs), as potent phagocytes engulf dead cells and present peptide 
      fragments of tumor antigens or pathogens derived from infected cells to naive 
      CD8(+) T-lymphocytes. Dendritic cells can also induce apoptosis in target cells, 
      thus getting an opportunity to sample their microenvironment. Here, we present 
      that the supernatants of LPS- or CL075-activated DCs induced cell death in 
      different cell lines, but during the differentiation to mature DCs, they lost 
      their cytotoxic potential. Dexamethasone-pre-treated tolerogenic DCs induced less 
      intensive death indicating that the tissue microenvironment can downregulate 
      DC-mediated killing. Exploring the signaling of DC-induced cell death, we 
      observed that the supernatant of activated DCs induced TNF-dependent cell death, 
      since TNF antagonist blocked the cytotoxic activity of DCs, contrary to 
      inhibitors of Fas and TRAIL receptors. We identified that the DC-induced killing 
      is at least partially a RIPK1-dependent process, as RIPK1 positive target cells 
      were more susceptible to DC-induced cell death than their RIPK1 deficient 
      counterparts. Moreover, both the elevated phosphorylation of RIPK1 and the 
      increase in RIPK1-caspase-8 interaction in target cells suggest that 
      RIPK1-mediated signals contribute to DC supernatant-induced cell death. We also 
      proved that the cytotoxic activity of DC-derived supernatant induced apoptosis in 
      the target cells and not necroptosis, as it was completely abrogated with the pan 
      caspase inhibitor (Z-VAD), while the necroptosis inhibitor (Nec-1) had no effect. 
      Our work revealed that the supernatant of activated DCs induces the apoptosis of 
      target cells in a RIPK1-dependent manner. This phenomenon could be relevant for 
      the initiation of cross-presentation and may broaden the plethora of cytotoxic 
      mechanisms acting against tumor cells.
CI  - Copyright (c) 2020 The Author(s). Published by Elsevier GmbH.. All rights reserved.
FAU - Varga, Zsofia
AU  - Varga Z
AD  - Department of Immunology, Faculty of Medicine, University of Debrecen, Debrecen, 
      Hungary; University of Debrecen, Doctoral School of Molecular Cellular and Immune 
      Biology, Debrecen, Hungary.
FAU - Racz, Evelin
AU  - Racz E
AD  - Department of Immunology, Faculty of Medicine, University of Debrecen, Debrecen, 
      Hungary.
FAU - Mazlo, Anett
AU  - Mazlo A
AD  - Department of Immunology, Faculty of Medicine, University of Debrecen, Debrecen, 
      Hungary; University of Debrecen, Doctoral School of Molecular Cellular and Immune 
      Biology, Debrecen, Hungary.
FAU - Korodi, Monika
AU  - Korodi M
AD  - University of Pecs, Doctoral School of Chemistry, Department of Chemistry, 
      Faculty of Sciences, Pecs, Hungary.
FAU - Szabo, Aniko
AU  - Szabo A
AD  - Department of Immunology, Faculty of Medicine, University of Debrecen, Debrecen, 
      Hungary.
FAU - Molnar, Tamas
AU  - Molnar T
AD  - Department of Immunology, Faculty of Medicine, University of Debrecen, Debrecen, 
      Hungary; University of Debrecen, Doctoral School of Molecular Cellular and Immune 
      Biology, Debrecen, Hungary.
FAU - Szoor, Arpad
AU  - Szoor A
AD  - Department of Biophysics and Cell Biology, Faculty of Medicine, University of 
      Debrecen, Debrecen, Hungary.
FAU - Vereb, Zoltan
AU  - Vereb Z
AD  - Regenerative Medicine and Cellular Pharmacology Laboratory (HECRIN), Department 
      of Dermatology and Allergology, University of Szeged, Szeged, Hungary; Institute 
      for Translational Medicine, University of Szeged, Szeged, Hungary.
FAU - Bacsi, Attila
AU  - Bacsi A
AD  - Department of Immunology, Faculty of Medicine, University of Debrecen, Debrecen, 
      Hungary.
FAU - Koncz, Gabor
AU  - Koncz G
AD  - Department of Immunology, Faculty of Medicine, University of Debrecen, Debrecen, 
      Hungary. Electronic address: konczgb@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201123
PL  - Netherlands
TA  - Immunobiology
JT  - Immunobiology
JID - 8002742
RN  - 0 (Caspase Inhibitors)
RN  - 0 (Oligopeptides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (benzyloxycarbonyl-valyl-alanyl-aspartic acid)
RN  - EC 2.7.11.1 (RIPK1 protein, human)
RN  - EC 2.7.11.1 (Receptor-Interacting Protein Serine-Threonine Kinases)
RN  - EC 3.4.22.- (Caspase 8)
SB  - IM
MH  - Apoptosis
MH  - Caspase 8/metabolism
MH  - Caspase Inhibitors/pharmacology
MH  - Cell Death
MH  - Cross-Priming
MH  - Cytotoxicity, Immunologic
MH  - Dendritic Cells/*immunology
MH  - HT29 Cells
MH  - Humans
MH  - Immune Tolerance
MH  - Neoplasms/*immunology
MH  - Oligopeptides/pharmacology
MH  - Receptor-Interacting Protein Serine-Threonine Kinases/*metabolism
MH  - Signal Transduction
MH  - Tumor Necrosis Factor-alpha/metabolism
OTO - NOTNLM
OT  - Cytotoxicity
OT  - Dendritic cells
OT  - Immune tolerance
OT  - Immunogenic cell death
OT  - RIPK1
EDAT- 2020/12/15 06:00
MHDA- 2022/01/27 06:00
CRDT- 2020/12/14 20:10
PHST- 2020/06/04 00:00 [received]
PHST- 2020/10/05 00:00 [revised]
PHST- 2020/11/18 00:00 [accepted]
PHST- 2020/12/15 06:00 [pubmed]
PHST- 2022/01/27 06:00 [medline]
PHST- 2020/12/14 20:10 [entrez]
AID - S0171-2985(20)30554-4 [pii]
AID - 10.1016/j.imbio.2020.152032 [doi]
PST - ppublish
SO  - Immunobiology. 2021 Jan;226(1):152032. doi: 10.1016/j.imbio.2020.152032. Epub 
      2020 Nov 23.