Immunological consequences of kidney cell death
| Autor: | Andreas Linkermann, Maysa Sarhan, Rainer Oberbauer, Christian Hugo, Anne von Mässenhausen |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research Programmed cell death Necrosis Necroptosis Immunology Apoptosis Autoimmunity Review Article Kidney Models Biological 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Immune system medicine Animals Humans lcsh:QH573-671 Caspase biology lcsh:Cytology business.industry Pyroptosis Cell Biology medicine.disease Transplant rejection Cell biology 030104 developmental biology 030220 oncology & carcinogenesis biology.protein medicine.symptom business Signal Transduction |
| Zdroj: | Cell Death & Disease Cell Death and Disease, Vol 9, Iss 2, Pp 1-15 (2018) |
| ISSN: | 2041-4889 |
| DOI: | 10.1038/s41419-017-0057-9 |
| Popis: | Death of renal cells is central to the pathophysiology of acute tubular necrosis, autoimmunity, necrotizing glomerulonephritis, cystic kidney disease, urosepsis, delayed graft function and transplant rejection. By means of regulated necrosis, immunogenic damage-associated molecular patterns (DAMPs) and highly reactive organelles such as lysosomes, peroxisomes and mitochondria are released from the dying cells, thereby causing an overwhelming immunologic response. The rupture of the plasma membrane exhibits the “point of no return” for the immunogenicity of regulated cell death, explaining why apoptosis, a highly organized cell death subroutine with long-lasting plasma membrane integrity, elicits hardly any immune response. Ferroptosis, an iron-dependent necrotic type cell death, results in the release of DAMPs and large amounts of lipid peroxides. In contrast, anti-inflammatory cytokines are actively released from cells that die by necroptosis, limiting the DAMP-induced immune response to a surrounding microenvironment, whereas at the same time, inflammasome-associated caspases drive maturation of intracellularly expressed interleukin-1β (IL-1β). In a distinct setting, additionally interleukin-18 (IL-18) is expressed during pyroptosis, initiated by gasdermin-mediated plasma membrane rupture. As all of these pathways are druggable, we provide an overview of regulated necrosis in kidney diseases with a focus on immunogenicity and potential therapeutic interventions. Key Points Regulated necrosis is a genetically determined process that contributes to acute kidney injury and causes antibody-mediated rejection (ABMR).Necroptosis, ferroptosis and pyroptosis are the best-studied pathways of regulated necrosis in acute kidney injury and transplantation.Necrotic cell death results in the release of DAMPs and is often prone to elicit an immune response.Failure to efficiently remove necrotic debris by LC3-associated phagocytosis (LAP) results in autoimmunity.During the process of kidney transplantation, necrotic cells are capable of priming memory B cells that may drive ABMR years after transplantation.Necroptosis, ferroptosis and pyroptosis can be therapeutically interfered with by small molecules. |
| Databáze: | OpenAIRE |
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