The NLRP3 inflammasome functions as a driver of the myelodysplastic syndrome phenotype.
Identifieur interne : 001611 ( Main/Exploration ); précédent : 001610; suivant : 001612The NLRP3 inflammasome functions as a driver of the myelodysplastic syndrome phenotype.
Auteurs : Ashley A. Basiorka ; Kathy L. Mcgraw ; Erika A. Eksioglu ; Xianghong Chen ; Joseph Johnson ; Ling Zhang [États-Unis] ; Qing Zhang ; Brittany A. Irvine ; Thomas Cluzeau [France] ; David A. Sallman ; Eric Padron ; Rami Komrokji ; Lubomir Sokol ; Rebecca C. Coll [Australie] ; Avril A B. Robertson [Australie] ; Matthew A. Cooper [Australie] ; John L. Cleveland ; Luke A. O'Neill [Irlande (pays)] ; Sheng Wei ; Alan F. ListSource :
- Blood [ 1528-0020 ] ; 2016.
Descripteurs français
- KwdFr :
- Animaux, Calgranuline B (métabolisme), Canaux ioniques (métabolisme), Cellules souches hématopoïétiques (anatomopathologie), Cellules souches hématopoïétiques (métabolisme), Espèces réactives de l'oxygène (métabolisme), Humains, Hématopoïèse, Inflammasomes (métabolisme), Mutation (génétique), NADPH oxidase (métabolisme), Ouverture et fermeture des portes des canaux ioniques, Phénotype, Protéine-3 de la famille des NLR contenant un domaine pyrine (métabolisme), Pyroptose, Souris transgéniques, Syndromes myélodysplasiques (anatomopathologie), Syndromes myélodysplasiques (métabolisme), Taille de la cellule, Test clonogénique, bêta-Caténine (métabolisme).
- MESH :
- anatomopathologie : Cellules souches hématopoïétiques, Syndromes myélodysplasiques.
- génétique : Mutation.
- métabolisme : Calgranuline B, Canaux ioniques, Cellules souches hématopoïétiques, Espèces réactives de l'oxygène, Inflammasomes, NADPH oxidase, Protéine-3 de la famille des NLR contenant un domaine pyrine, Syndromes myélodysplasiques, bêta-Caténine.
- Animaux, Humains, Hématopoïèse, Ouverture et fermeture des portes des canaux ioniques, Phénotype, Pyroptose, Souris transgéniques, Taille de la cellule, Test clonogénique.
English descriptors
- KwdEn :
- Animals, Calgranulin B (metabolism), Cell Size, Colony-Forming Units Assay, Hematopoiesis, Hematopoietic Stem Cells (metabolism), Hematopoietic Stem Cells (pathology), Humans, Inflammasomes (metabolism), Ion Channel Gating, Ion Channels (metabolism), Mice, Transgenic, Mutation (genetics), Myelodysplastic Syndromes (metabolism), Myelodysplastic Syndromes (pathology), NADPH Oxidase (metabolism), NLR Family, Pyrin Domain-Containing 3 Protein (metabolism), Phenotype, Pyroptosis, Reactive Oxygen Species (metabolism), beta Catenin (metabolism).
- MESH :
- chemical , metabolism : Calgranulin B, Inflammasomes, Ion Channels, NADPH Oxidase, NLR Family, Pyrin Domain-Containing 3 Protein, Reactive Oxygen Species, beta Catenin.
- genetics : Mutation.
- metabolism : Hematopoietic Stem Cells, Myelodysplastic Syndromes.
- pathology : Hematopoietic Stem Cells, Myelodysplastic Syndromes.
- Animals, Cell Size, Colony-Forming Units Assay, Hematopoiesis, Humans, Ion Channel Gating, Mice, Transgenic, Phenotype, Pyroptosis.
Abstract
Despite genetic heterogeneity, myelodysplastic syndromes (MDSs) share features of cytological dysplasia and ineffective hematopoiesis. We report that a hallmark of MDSs is activation of the NLRP3 inflammasome, which drives clonal expansion and pyroptotic cell death. Independent of genotype, MDS hematopoietic stem and progenitor cells (HSPCs) overexpress inflammasome proteins and manifest activated NLRP3 complexes that direct activation of caspase-1, generation of interleukin-1β (IL-1β) and IL-18, and pyroptotic cell death. Mechanistically, pyroptosis is triggered by the alarmin S100A9 that is found in excess in MDS HSPCs and bone marrow plasma. Further, like somatic gene mutations, S100A9-induced signaling activates NADPH oxidase (NOX), increasing levels of reactive oxygen species (ROS) that initiate cation influx, cell swelling, and β-catenin activation. Notably, knockdown of NLRP3 or caspase-1, neutralization of S100A9, and pharmacologic inhibition of NLRP3 or NOX suppress pyroptosis, ROS generation, and nuclear β-catenin in MDSs and are sufficient to restore effective hematopoiesis. Thus, alarmins and founder gene mutations in MDSs license a common redox-sensitive inflammasome circuit, which suggests new avenues for therapeutic intervention.
DOI: 10.1182/blood-2016-07-730556
PubMed: 27737891
Affiliations:
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Lee Moffitt Cancer Center, Tampa, FL.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Floride</region></placeName><wicri:cityArea>Department of Hematopathology, H. Lee Moffitt Cancer Center, Tampa</wicri:cityArea></affiliation></author><author><name sortKey="Zhang, Qing" sort="Zhang, Qing" uniqKey="Zhang Q" first="Qing" last="Zhang">Qing Zhang</name><affiliation><nlm:affiliation>Department of Malignant Hematology.</nlm:affiliation><wicri:noCountry code="no comma">Department of Malignant Hematology.</wicri:noCountry></affiliation></author><author><name sortKey="Irvine, Brittany A" sort="Irvine, Brittany A" uniqKey="Irvine B" first="Brittany A" last="Irvine">Brittany A. Irvine</name><affiliation><nlm:affiliation>Department of Malignant Hematology.</nlm:affiliation><wicri:noCountry code="no comma">Department of Malignant Hematology.</wicri:noCountry></affiliation></author><author><name sortKey="Cluzeau, Thomas" sort="Cluzeau, Thomas" uniqKey="Cluzeau T" first="Thomas" last="Cluzeau">Thomas Cluzeau</name><affiliation wicri:level="3"><nlm:affiliation>Department of Hematology, Centre Hospitalier Universitaire de Nice, Nice, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Hematology, Centre Hospitalier Universitaire de Nice, Nice</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Nice</settlement></placeName></affiliation></author><author><name sortKey="Sallman, David A" sort="Sallman, David A" uniqKey="Sallman D" first="David A" last="Sallman">David A. Sallman</name><affiliation><nlm:affiliation>Department of Malignant Hematology.</nlm:affiliation><wicri:noCountry code="no comma">Department of Malignant Hematology.</wicri:noCountry></affiliation></author><author><name sortKey="Padron, Eric" sort="Padron, Eric" uniqKey="Padron E" first="Eric" last="Padron">Eric Padron</name><affiliation><nlm:affiliation>Department of Malignant Hematology.</nlm:affiliation><wicri:noCountry code="no comma">Department of Malignant Hematology.</wicri:noCountry></affiliation></author><author><name sortKey="Komrokji, Rami" sort="Komrokji, Rami" uniqKey="Komrokji R" first="Rami" last="Komrokji">Rami Komrokji</name><affiliation><nlm:affiliation>Department of Malignant Hematology.</nlm:affiliation><wicri:noCountry code="no comma">Department of Malignant Hematology.</wicri:noCountry></affiliation></author><author><name sortKey="Sokol, Lubomir" sort="Sokol, Lubomir" uniqKey="Sokol L" first="Lubomir" last="Sokol">Lubomir Sokol</name><affiliation><nlm:affiliation>Department of Malignant Hematology.</nlm:affiliation><wicri:noCountry code="no comma">Department of Malignant Hematology.</wicri:noCountry></affiliation></author><author><name sortKey="Coll, Rebecca C" sort="Coll, Rebecca C" uniqKey="Coll R" first="Rebecca C" last="Coll">Rebecca C. Coll</name><affiliation wicri:level="1"><nlm:affiliation>Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Institute for Molecular Bioscience, University of Queensland, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Robertson, Avril A B" sort="Robertson, Avril A B" uniqKey="Robertson A" first="Avril A B" last="Robertson">Avril A B. Robertson</name><affiliation wicri:level="1"><nlm:affiliation>Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Institute for Molecular Bioscience, University of Queensland, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Cooper, Matthew A" sort="Cooper, Matthew A" uniqKey="Cooper M" first="Matthew A" last="Cooper">Matthew A. Cooper</name><affiliation wicri:level="1"><nlm:affiliation>Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Institute for Molecular Bioscience, University of Queensland, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Cleveland, John L" sort="Cleveland, John L" uniqKey="Cleveland J" first="John L" last="Cleveland">John L. Cleveland</name><affiliation><nlm:affiliation>Department of Tumor Biology, H. Lee Moffitt Cancer Center, Tampa, FL; and.</nlm:affiliation><wicri:noCountry code="subField">FL; and</wicri:noCountry></affiliation></author><author><name sortKey="O Neill, Luke A" sort="O Neill, Luke A" uniqKey="O Neill L" first="Luke A" last="O'Neill">Luke A. O'Neill</name><affiliation wicri:level="1"><nlm:affiliation>Trinity Biomedical Sciences Institute, School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland.</nlm:affiliation><country xml:lang="fr">Irlande (pays)</country><wicri:regionArea>Trinity Biomedical Sciences Institute, School of Biochemistry and Immunology, Trinity College Dublin, Dublin</wicri:regionArea><wicri:noRegion>Dublin</wicri:noRegion></affiliation></author><author><name sortKey="Wei, Sheng" sort="Wei, Sheng" uniqKey="Wei S" first="Sheng" last="Wei">Sheng Wei</name><affiliation><nlm:affiliation>Department of Immunology.</nlm:affiliation><wicri:noCountry code="no comma">Department of Immunology.</wicri:noCountry></affiliation></author><author><name sortKey="List, Alan F" sort="List, Alan F" uniqKey="List A" first="Alan F" last="List">Alan F. 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Basiorka</name><affiliation><nlm:affiliation>Cancer Biology Ph.D. Program, Department of Malignant Hematology.</nlm:affiliation><wicri:noCountry code="subField">Department of Malignant Hematology</wicri:noCountry></affiliation></author><author><name sortKey="Mcgraw, Kathy L" sort="Mcgraw, Kathy L" uniqKey="Mcgraw K" first="Kathy L" last="Mcgraw">Kathy L. Mcgraw</name><affiliation><nlm:affiliation>Department of Malignant Hematology.</nlm:affiliation><wicri:noCountry code="no comma">Department of Malignant Hematology.</wicri:noCountry></affiliation></author><author><name sortKey="Eksioglu, Erika A" sort="Eksioglu, Erika A" uniqKey="Eksioglu E" first="Erika A" last="Eksioglu">Erika A. Eksioglu</name><affiliation><nlm:affiliation>Department of Immunology.</nlm:affiliation><wicri:noCountry code="no comma">Department of Immunology.</wicri:noCountry></affiliation></author><author><name sortKey="Chen, Xianghong" sort="Chen, Xianghong" uniqKey="Chen X" first="Xianghong" last="Chen">Xianghong Chen</name><affiliation><nlm:affiliation>Department of Immunology.</nlm:affiliation><wicri:noCountry code="no comma">Department of Immunology.</wicri:noCountry></affiliation></author><author><name sortKey="Johnson, Joseph" sort="Johnson, Joseph" uniqKey="Johnson J" first="Joseph" last="Johnson">Joseph Johnson</name><affiliation><nlm:affiliation>Analytic Microscopy Core Facility, and.</nlm:affiliation><wicri:noCountry code="subField">and</wicri:noCountry></affiliation></author><author><name sortKey="Zhang, Ling" sort="Zhang, Ling" uniqKey="Zhang L" first="Ling" last="Zhang">Ling Zhang</name><affiliation wicri:level="2"><nlm:affiliation>Department of Hematopathology, H. Lee Moffitt Cancer Center, Tampa, FL.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Floride</region></placeName><wicri:cityArea>Department of Hematopathology, H. Lee Moffitt Cancer Center, Tampa</wicri:cityArea></affiliation></author><author><name sortKey="Zhang, Qing" sort="Zhang, Qing" uniqKey="Zhang Q" first="Qing" last="Zhang">Qing Zhang</name><affiliation><nlm:affiliation>Department of Malignant Hematology.</nlm:affiliation><wicri:noCountry code="no comma">Department of Malignant Hematology.</wicri:noCountry></affiliation></author><author><name sortKey="Irvine, Brittany A" sort="Irvine, Brittany A" uniqKey="Irvine B" first="Brittany A" last="Irvine">Brittany A. Irvine</name><affiliation><nlm:affiliation>Department of Malignant Hematology.</nlm:affiliation><wicri:noCountry code="no comma">Department of Malignant Hematology.</wicri:noCountry></affiliation></author><author><name sortKey="Cluzeau, Thomas" sort="Cluzeau, Thomas" uniqKey="Cluzeau T" first="Thomas" last="Cluzeau">Thomas Cluzeau</name><affiliation wicri:level="3"><nlm:affiliation>Department of Hematology, Centre Hospitalier Universitaire de Nice, Nice, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Hematology, Centre Hospitalier Universitaire de Nice, Nice</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Nice</settlement></placeName></affiliation></author><author><name sortKey="Sallman, David A" sort="Sallman, David A" uniqKey="Sallman D" first="David A" last="Sallman">David A. Sallman</name><affiliation><nlm:affiliation>Department of Malignant Hematology.</nlm:affiliation><wicri:noCountry code="no comma">Department of Malignant Hematology.</wicri:noCountry></affiliation></author><author><name sortKey="Padron, Eric" sort="Padron, Eric" uniqKey="Padron E" first="Eric" last="Padron">Eric Padron</name><affiliation><nlm:affiliation>Department of Malignant Hematology.</nlm:affiliation><wicri:noCountry code="no comma">Department of Malignant Hematology.</wicri:noCountry></affiliation></author><author><name sortKey="Komrokji, Rami" sort="Komrokji, Rami" uniqKey="Komrokji R" first="Rami" last="Komrokji">Rami Komrokji</name><affiliation><nlm:affiliation>Department of Malignant Hematology.</nlm:affiliation><wicri:noCountry code="no comma">Department of Malignant Hematology.</wicri:noCountry></affiliation></author><author><name sortKey="Sokol, Lubomir" sort="Sokol, Lubomir" uniqKey="Sokol L" first="Lubomir" last="Sokol">Lubomir Sokol</name><affiliation><nlm:affiliation>Department of Malignant Hematology.</nlm:affiliation><wicri:noCountry code="no comma">Department of Malignant Hematology.</wicri:noCountry></affiliation></author><author><name sortKey="Coll, Rebecca C" sort="Coll, Rebecca C" uniqKey="Coll R" first="Rebecca C" last="Coll">Rebecca C. Coll</name><affiliation wicri:level="1"><nlm:affiliation>Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Institute for Molecular Bioscience, University of Queensland, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Robertson, Avril A B" sort="Robertson, Avril A B" uniqKey="Robertson A" first="Avril A B" last="Robertson">Avril A B. Robertson</name><affiliation wicri:level="1"><nlm:affiliation>Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Institute for Molecular Bioscience, University of Queensland, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Cooper, Matthew A" sort="Cooper, Matthew A" uniqKey="Cooper M" first="Matthew A" last="Cooper">Matthew A. Cooper</name><affiliation wicri:level="1"><nlm:affiliation>Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Institute for Molecular Bioscience, University of Queensland, Brisbane</wicri:regionArea><wicri:noRegion>Brisbane</wicri:noRegion></affiliation></author><author><name sortKey="Cleveland, John L" sort="Cleveland, John L" uniqKey="Cleveland J" first="John L" last="Cleveland">John L. Cleveland</name><affiliation><nlm:affiliation>Department of Tumor Biology, H. Lee Moffitt Cancer Center, Tampa, FL; and.</nlm:affiliation><wicri:noCountry code="subField">FL; and</wicri:noCountry></affiliation></author><author><name sortKey="O Neill, Luke A" sort="O Neill, Luke A" uniqKey="O Neill L" first="Luke A" last="O'Neill">Luke A. O'Neill</name><affiliation wicri:level="1"><nlm:affiliation>Trinity Biomedical Sciences Institute, School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland.</nlm:affiliation><country xml:lang="fr">Irlande (pays)</country><wicri:regionArea>Trinity Biomedical Sciences Institute, School of Biochemistry and Immunology, Trinity College Dublin, Dublin</wicri:regionArea><wicri:noRegion>Dublin</wicri:noRegion></affiliation></author><author><name sortKey="Wei, Sheng" sort="Wei, Sheng" uniqKey="Wei S" first="Sheng" last="Wei">Sheng Wei</name><affiliation><nlm:affiliation>Department of Immunology.</nlm:affiliation><wicri:noCountry code="no comma">Department of Immunology.</wicri:noCountry></affiliation></author><author><name sortKey="List, Alan F" sort="List, Alan F" uniqKey="List A" first="Alan F" last="List">Alan F. List</name><affiliation><nlm:affiliation>Department of Malignant Hematology.</nlm:affiliation><wicri:noCountry code="no comma">Department of Malignant Hematology.</wicri:noCountry></affiliation></author></analytic><series><title level="j">Blood</title><idno type="eISSN">1528-0020</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Calgranulin B (metabolism)</term><term>Cell Size</term><term>Colony-Forming Units Assay</term><term>Hematopoiesis</term><term>Hematopoietic Stem Cells (metabolism)</term><term>Hematopoietic Stem Cells (pathology)</term><term>Humans</term><term>Inflammasomes (metabolism)</term><term>Ion Channel Gating</term><term>Ion Channels (metabolism)</term><term>Mice, Transgenic</term><term>Mutation (genetics)</term><term>Myelodysplastic Syndromes (metabolism)</term><term>Myelodysplastic Syndromes (pathology)</term><term>NADPH Oxidase (metabolism)</term><term>NLR Family, Pyrin Domain-Containing 3 Protein (metabolism)</term><term>Phenotype</term><term>Pyroptosis</term><term>Reactive Oxygen Species (metabolism)</term><term>beta Catenin (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Calgranuline B (métabolisme)</term><term>Canaux ioniques (métabolisme)</term><term>Cellules souches hématopoïétiques (anatomopathologie)</term><term>Cellules souches hématopoïétiques (métabolisme)</term><term>Espèces réactives de l'oxygène (métabolisme)</term><term>Humains</term><term>Hématopoïèse</term><term>Inflammasomes (métabolisme)</term><term>Mutation (génétique)</term><term>NADPH oxidase (métabolisme)</term><term>Ouverture et fermeture des portes des canaux ioniques</term><term>Phénotype</term><term>Protéine-3 de la famille des NLR contenant un domaine pyrine (métabolisme)</term><term>Pyroptose</term><term>Souris transgéniques</term><term>Syndromes myélodysplasiques (anatomopathologie)</term><term>Syndromes myélodysplasiques (métabolisme)</term><term>Taille de la cellule</term><term>Test clonogénique</term><term>bêta-Caténine (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Calgranulin B</term><term>Inflammasomes</term><term>Ion Channels</term><term>NADPH Oxidase</term><term>NLR Family, Pyrin Domain-Containing 3 Protein</term><term>Reactive Oxygen Species</term><term>beta Catenin</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Cellules souches hématopoïétiques</term><term>Syndromes myélodysplasiques</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Mutation</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Mutation</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Hematopoietic Stem Cells</term><term>Myelodysplastic Syndromes</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Calgranuline B</term><term>Canaux ioniques</term><term>Cellules souches hématopoïétiques</term><term>Espèces réactives de l'oxygène</term><term>Inflammasomes</term><term>NADPH oxidase</term><term>Protéine-3 de la famille des NLR contenant un domaine pyrine</term><term>Syndromes myélodysplasiques</term><term>bêta-Caténine</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Hematopoietic Stem Cells</term><term>Myelodysplastic Syndromes</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Size</term><term>Colony-Forming Units Assay</term><term>Hematopoiesis</term><term>Humans</term><term>Ion Channel Gating</term><term>Mice, Transgenic</term><term>Phenotype</term><term>Pyroptosis</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Humains</term><term>Hématopoïèse</term><term>Ouverture et fermeture des portes des canaux ioniques</term><term>Phénotype</term><term>Pyroptose</term><term>Souris transgéniques</term><term>Taille de la cellule</term><term>Test clonogénique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Despite genetic heterogeneity, myelodysplastic syndromes (MDSs) share features of cytological dysplasia and ineffective hematopoiesis. We report that a hallmark of MDSs is activation of the NLRP3 inflammasome, which drives clonal expansion and pyroptotic cell death. Independent of genotype, MDS hematopoietic stem and progenitor cells (HSPCs) overexpress inflammasome proteins and manifest activated NLRP3 complexes that direct activation of caspase-1, generation of interleukin-1β (IL-1β) and IL-18, and pyroptotic cell death. Mechanistically, pyroptosis is triggered by the alarmin S100A9 that is found in excess in MDS HSPCs and bone marrow plasma. Further, like somatic gene mutations, S100A9-induced signaling activates NADPH oxidase (NOX), increasing levels of reactive oxygen species (ROS) that initiate cation influx, cell swelling, and β-catenin activation. Notably, knockdown of NLRP3 or caspase-1, neutralization of S100A9, and pharmacologic inhibition of NLRP3 or NOX suppress pyroptosis, ROS generation, and nuclear β-catenin in MDSs and are sufficient to restore effective hematopoiesis. Thus, alarmins and founder gene mutations in MDSs license a common redox-sensitive inflammasome circuit, which suggests new avenues for therapeutic intervention.</div></front></TEI><affiliations><list><country><li>Australie</li><li>France</li><li>Irlande (pays)</li><li>États-Unis</li></country><region><li>Floride</li><li>Provence-Alpes-Côte d'Azur</li></region><settlement><li>Nice</li></settlement></list><tree><noCountry><name sortKey="Basiorka, Ashley A" sort="Basiorka, Ashley A" uniqKey="Basiorka A" first="Ashley A" last="Basiorka">Ashley A. Basiorka</name><name sortKey="Chen, Xianghong" sort="Chen, Xianghong" uniqKey="Chen X" first="Xianghong" last="Chen">Xianghong Chen</name><name sortKey="Cleveland, John L" sort="Cleveland, John L" uniqKey="Cleveland J" first="John L" last="Cleveland">John L. Cleveland</name><name sortKey="Eksioglu, Erika A" sort="Eksioglu, Erika A" uniqKey="Eksioglu E" first="Erika A" last="Eksioglu">Erika A. Eksioglu</name><name sortKey="Irvine, Brittany A" sort="Irvine, Brittany A" uniqKey="Irvine B" first="Brittany A" last="Irvine">Brittany A. Irvine</name><name sortKey="Johnson, Joseph" sort="Johnson, Joseph" uniqKey="Johnson J" first="Joseph" last="Johnson">Joseph Johnson</name><name sortKey="Komrokji, Rami" sort="Komrokji, Rami" uniqKey="Komrokji R" first="Rami" last="Komrokji">Rami Komrokji</name><name sortKey="List, Alan F" sort="List, Alan F" uniqKey="List A" first="Alan F" last="List">Alan F. List</name><name sortKey="Mcgraw, Kathy L" sort="Mcgraw, Kathy L" uniqKey="Mcgraw K" first="Kathy L" last="Mcgraw">Kathy L. Mcgraw</name><name sortKey="Padron, Eric" sort="Padron, Eric" uniqKey="Padron E" first="Eric" last="Padron">Eric Padron</name><name sortKey="Sallman, David A" sort="Sallman, David A" uniqKey="Sallman D" first="David A" last="Sallman">David A. Sallman</name><name sortKey="Sokol, Lubomir" sort="Sokol, Lubomir" uniqKey="Sokol L" first="Lubomir" last="Sokol">Lubomir Sokol</name><name sortKey="Wei, Sheng" sort="Wei, Sheng" uniqKey="Wei S" first="Sheng" last="Wei">Sheng Wei</name><name sortKey="Zhang, Qing" sort="Zhang, Qing" uniqKey="Zhang Q" first="Qing" last="Zhang">Qing Zhang</name></noCountry><country name="États-Unis"><region name="Floride"><name sortKey="Zhang, Ling" sort="Zhang, Ling" uniqKey="Zhang L" first="Ling" last="Zhang">Ling Zhang</name></region></country><country name="France"><region name="Provence-Alpes-Côte d'Azur"><name sortKey="Cluzeau, Thomas" sort="Cluzeau, Thomas" uniqKey="Cluzeau T" first="Thomas" last="Cluzeau">Thomas Cluzeau</name></region></country><country name="Australie"><noRegion><name sortKey="Coll, Rebecca C" sort="Coll, Rebecca C" uniqKey="Coll R" first="Rebecca C" last="Coll">Rebecca C. Coll</name></noRegion><name sortKey="Cooper, Matthew A" sort="Cooper, Matthew A" uniqKey="Cooper M" first="Matthew A" last="Cooper">Matthew A. Cooper</name><name sortKey="Robertson, Avril A B" sort="Robertson, Avril A B" uniqKey="Robertson A" first="Avril A B" last="Robertson">Avril A B. Robertson</name></country><country name="Irlande (pays)"><noRegion><name sortKey="O Neill, Luke A" sort="O Neill, Luke A" uniqKey="O Neill L" first="Luke A" last="O'Neill">Luke A. O'Neill</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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