Cytotoxic activity of human dendritic cells induces RIPK1-dependent cell death
| Autor: | Tamás Molnár, Mónika Korodi, Gábor Koncz, Evelin Rácz, Árpád Szöőr, Zoltán Veréb, Aniko Szabo, Zsófia Varga, Attila Bacsi, Anett Mázló |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Cytotoxicity
Immunologic 0301 basic medicine Programmed cell death Necroptosis Immunology Apoptosis Immune tolerance 03 medical and health sciences Cross-Priming 0302 clinical medicine Neoplasms Immune Tolerance Humans Immunology and Allergy Cytotoxic T cell Caspase 8 Cell Death Tumor Necrosis Factor-alpha Chemistry Dendritic Cells Hematology Caspase Inhibitors Cell biology 030104 developmental biology Cell culture Receptor-Interacting Protein Serine-Threonine Kinases Immunogenic cell death HT29 Cells Oligopeptides CD8 Signal Transduction 030215 immunology |
| Zdroj: | Immunobiology. 226:152032 |
| ISSN: | 0171-2985 |
| DOI: | 10.1016/j.imbio.2020.152032 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect