Project: Mechanisms of ferroptosis mediated immunoregulation
2022-01-01 – 2025-12-31
- Abstract
Ferroptosis is an iron-dependent, necrotic type of cell death driven by lipid peroxidation (LPO) in the plasma membrane. The efficient killing of cancer cells makes ferroptosis a compelling strategy for novel therapy treatments, but the relationship between ferroptosis and the immune system still form a blanc sheet for further research. We found that ferroptotic cells, despite abundant release of damage associated molecular patterns (DAMPs), cytokines and interferons, do not induce an immunological protection against cancer cells, in contrast to necrotic or other known ‘immunogenic’ cell death modalities. We found that dendritic cells exposed to ferroptotic cells fail to support antigen cross presentation, a prerequisite for an adaptive immune response. Oxygen and iron are Earth’s most abundant elements by number of atoms and by mass, respectively, and are at the core of the regulation and execution of ferroptosis. The central hypothesis of the project is that in a world full of oxygen and iron the occurrence of ferroptosis may have resulted in the coevolution of subroutine mechanisms that prevent strong host-mediated responses against the consequences of occasionally, accidently or pathologically occurring ferroptosis. In this project, we aim to identify the tolerance inducing factors (TIFs) and mechanisms how ferroptotic cells instruct dendritic cells (DCs) to tolerance as a way to avoid overreaction by sporadic, infection or trauma induced ferroptosis.
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- Journal Article
- open access
A guide to the expanding field of extracellular vesicles and their release in regulated cell death programs
(2023) FEBS JOURNAL. -
- Journal Article
- A1
- open access
Systematic compositional analysis of exosomal extracellular vesicles produced by cells undergoing apoptosis, necroptosis and ferroptosis
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- Journal Article
- A1
- open access
Ferroptosis contributes to multiple sclerosis and its pharmacological targeting suppresses experimental disease progression
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- Journal Article
- A1
- open access
Molecular mechanisms of nemorosone-induced ferroptosis in cancer cells
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- Journal Article
- A1
- open access
RIPK1 kinase-dependent inflammation and cell death contribute to the pathogenesis of COPD
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- Journal Article
- A1
- open access
Pore-forming proteins as drivers of membrane permeabilization in cell death pathways
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- Journal Article
- A1
- open access
Tyramide signal amplification for the immunofluorescent staining of ZBP1-dependent phosphorylation of RIPK3 and MLKL after HSV-1 infection in human cells
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Spectrally tunable Förster resonance energy transfer-based biosensors using organic dye grafting
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- Journal Article
- A1
- open access
ADAR1 prevents autoinflammation by suppressing spontaneous ZBP1 activation
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- Journal Article
- A1
- open access
Cancer cells dying from ferroptosis impede dendritic cell-mediated anti-tumor immunity