Chronic inflammation in conditions associated with a deficient clearance of dying and dead cells, their remnants, and intracellular constituents

In multicellular organisms, states with a high degree of tissue turnover like embryogenesis, development, and adult tissue homeostasis need an instantaneous, tightly regulated and immunologically silent clearance of these dying cells to ensure appropriate development of the embryo and adult tissue r...

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Hlavní autoři: Martin Herrmann, Christian Berens, Luis Enrique Munoz, Kirsten Lauber, Udo S. Gaipl
Médium: Online
Jazyk:angličtina
Vydáno: Frontiers Media SA 2021
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author Martin Herrmann
Christian Berens
Luis Enrique Munoz
Kirsten Lauber
Udo S. Gaipl
author_browse Christian Berens
Kirsten Lauber
Luis Enrique Munoz
Martin Herrmann
Udo S. Gaipl
author_facet Martin Herrmann
Christian Berens
Luis Enrique Munoz
Kirsten Lauber
Udo S. Gaipl
author_sort Martin Herrmann
collection Directory of Open Access Books
description In multicellular organisms, states with a high degree of tissue turnover like embryogenesis, development, and adult tissue homeostasis need an instantaneous, tightly regulated and immunologically silent clearance of these dying cells to ensure appropriate development of the embryo and adult tissue remodelling. The proper and swift clearance of apoptotic cells is essential to prevent cellular leakage of damage associated molecular patterns (DAMPs) which would lead to the stimulation of inflammatory cytokine responses. In addition to the clearance of apoptotic cells (efferocytosis), backup mechanisms are required to cope with DAMPs (HMGB-1, DNA, RNA, S100 molecules, ATP and adenosine) and other intracellular material (uric acid, intracellular proteins and their aggregates) released from cells, that were not properly cleared and have entered the stage of secondary necrosis. Furthermore, under certain pathologic conditions (e.g. gout, cancer, diabetes) non-apoptotic cell death may transiently occur (NETosis, necroptosis, pyroptosis) which generates material that also has to be cleared to avoid overloading tissues with non-functional cellular waste. Efficient efferocytosis is therefore indispensable for normal tissue turnover and homeostasis. The characterization of various signalling pathways that regulate this complex and evolutionary conserved process has shed light on new pathogenetic mechanisms of many diseases. Impaired clearance promotes initiation of autoimmunity as well as the perpetuation of chronic inflammation, but may also foster anti-tumor immunity under certain microenvironmental conditions. Immunological tolerance is continuously being challenged by the presence of post-apoptotic remnants in peripheral lymphoid tissues. Besides the autoimmune phenotype of chronic inflammatory rheumatoid disorders a plethora of pathologies have been associated with defects in genes involved in clearance, e.g. atherosclerosis, cancer, gout, diabetes, some forms of blindness, neuropathy, schizophrenia and Alzheimer’s disease. The main goal of this research topic is to collect contributions from various disciplines committed to studying pathogenetic mechanisms of the aforementioned disorders and dealing with alterations in the clearance of dying and dead cells, their remnants, and their constituents that leak out after membrane rupture. Integrating the combined collection of knowledge on efferocytosis and clearance of dead cells and their derived waste from different fields of research in physiology and pathophysiology could improve the molecular understanding of these increasingly prevalent diseases and may ultimately result in new therapeutic strategies.
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spelling doab-20.500.12854ir-431902024-03-31T13:11:16Z Chronic inflammation in conditions associated with a deficient clearance of dying and dead cells, their remnants, and intracellular constituents Martin Herrmann Christian Berens Luis Enrique Munoz Kirsten Lauber Udo S. Gaipl R5-920 RC581-607 Autoimmunity NETs Efferocytosis Inflammation cell-remnants Phagocytosis Apoptosis Cancer Asthma thema EDItEUR::M Medicine and Nursing In multicellular organisms, states with a high degree of tissue turnover like embryogenesis, development, and adult tissue homeostasis need an instantaneous, tightly regulated and immunologically silent clearance of these dying cells to ensure appropriate development of the embryo and adult tissue remodelling. The proper and swift clearance of apoptotic cells is essential to prevent cellular leakage of damage associated molecular patterns (DAMPs) which would lead to the stimulation of inflammatory cytokine responses. In addition to the clearance of apoptotic cells (efferocytosis), backup mechanisms are required to cope with DAMPs (HMGB-1, DNA, RNA, S100 molecules, ATP and adenosine) and other intracellular material (uric acid, intracellular proteins and their aggregates) released from cells, that were not properly cleared and have entered the stage of secondary necrosis. Furthermore, under certain pathologic conditions (e.g. gout, cancer, diabetes) non-apoptotic cell death may transiently occur (NETosis, necroptosis, pyroptosis) which generates material that also has to be cleared to avoid overloading tissues with non-functional cellular waste. Efficient efferocytosis is therefore indispensable for normal tissue turnover and homeostasis. The characterization of various signalling pathways that regulate this complex and evolutionary conserved process has shed light on new pathogenetic mechanisms of many diseases. Impaired clearance promotes initiation of autoimmunity as well as the perpetuation of chronic inflammation, but may also foster anti-tumor immunity under certain microenvironmental conditions. Immunological tolerance is continuously being challenged by the presence of post-apoptotic remnants in peripheral lymphoid tissues. Besides the autoimmune phenotype of chronic inflammatory rheumatoid disorders a plethora of pathologies have been associated with defects in genes involved in clearance, e.g. atherosclerosis, cancer, gout, diabetes, some forms of blindness, neuropathy, schizophrenia and Alzheimer’s disease. The main goal of this research topic is to collect contributions from various disciplines committed to studying pathogenetic mechanisms of the aforementioned disorders and dealing with alterations in the clearance of dying and dead cells, their remnants, and their constituents that leak out after membrane rupture. Integrating the combined collection of knowledge on efferocytosis and clearance of dead cells and their derived waste from different fields of research in physiology and pathophysiology could improve the molecular understanding of these increasingly prevalent diseases and may ultimately result in new therapeutic strategies. 2021-02-11T09:51:20Z 2021-02-11T09:51:20Z 2016-08-16 10:34:25 2015 book 19509 16648714 9782889196012 https://directory.doabooks.org/handle/20.500.12854/43190 eng Frontiers Research Topics image/jpeg Attribution 4.0 International http://www.frontiersin.org/books/Chronic_Inflammation_in_Conditions_Associated_with_a_Deficient_Clearance_of_Dying_and_Dead_Cells_th/671#nogo http://journal.frontiersin.org/researchtopic/2209/chronic-inflammation-in-conditions-associated-with-a-deficient-clearance-of-dying-and-dead-cells-the Frontiers Media SA 10.3389/978-2-88919-601-2 10.3389/978-2-88919-601-2 bf5ce210-e72e-4860-ba9b-c305640ff3ae 9782889196012 73 open access
spellingShingle R5-920
RC581-607
Autoimmunity
NETs
Efferocytosis
Inflammation
cell-remnants
Phagocytosis
Apoptosis
Cancer
Asthma
thema EDItEUR::M Medicine and Nursing
Martin Herrmann
Christian Berens
Luis Enrique Munoz
Kirsten Lauber
Udo S. Gaipl
Chronic inflammation in conditions associated with a deficient clearance of dying and dead cells, their remnants, and intracellular constituents
title Chronic inflammation in conditions associated with a deficient clearance of dying and dead cells, their remnants, and intracellular constituents
title_full Chronic inflammation in conditions associated with a deficient clearance of dying and dead cells, their remnants, and intracellular constituents
title_fullStr Chronic inflammation in conditions associated with a deficient clearance of dying and dead cells, their remnants, and intracellular constituents
title_full_unstemmed Chronic inflammation in conditions associated with a deficient clearance of dying and dead cells, their remnants, and intracellular constituents
title_short Chronic inflammation in conditions associated with a deficient clearance of dying and dead cells, their remnants, and intracellular constituents
title_sort chronic inflammation in conditions associated with a deficient clearance of dying and dead cells their remnants and intracellular constituents
topic R5-920
RC581-607
Autoimmunity
NETs
Efferocytosis
Inflammation
cell-remnants
Phagocytosis
Apoptosis
Cancer
Asthma
thema EDItEUR::M Medicine and Nursing
topic_facet R5-920
RC581-607
Autoimmunity
NETs
Efferocytosis
Inflammation
cell-remnants
Phagocytosis
Apoptosis
Cancer
Asthma
thema EDItEUR::M Medicine and Nursing
url 19509
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