The IRE1 endoplasmic reticulum stress sensor activates natural killer cell immunity in part by regulating c-Myc.
Identifieur interne : 000205 ( Main/Exploration ); précédent : 000204; suivant : 000206The IRE1 endoplasmic reticulum stress sensor activates natural killer cell immunity in part by regulating c-Myc.
Auteurs : Han Dong [États-Unis] ; Nicholas M. Adams [États-Unis] ; Yichi Xu [États-Unis] ; Jin Cao [États-Unis] ; David S J. Allan [États-Unis] ; James R. Carlyle [Canada] ; Xi Chen [États-Unis] ; Joseph C. Sun [États-Unis] ; Laurie H. Glimcher [États-Unis]Source :
- Nature immunology [ 1529-2916 ] ; 2019.
Descripteurs français
- KwdFr :
- Activation des lymphocytes (immunologie), Animaux (MeSH), Cellules tueuses naturelles (immunologie), Cellules tueuses naturelles (métabolisme), Cytotoxicité immunologique (MeSH), Endoribonucleases (génétique), Gènes myc (MeSH), Humains (MeSH), Immunité (génétique), Interactions hôte-pathogène (immunologie), Marqueurs biologiques (MeSH), Mitochondries (métabolisme), Mélanome expérimental (MeSH), Phosphorylation oxydative (MeSH), Protein-Serine-Threonine Kinases (génétique), Protéine-1 liant la boite X (métabolisme), Régulation de l'expression des gènes (MeSH), Souris (MeSH), Souris knockout (MeSH), Stress du réticulum endoplasmique (génétique), Survie cellulaire (génétique), Survie cellulaire (immunologie), Transduction du signal (MeSH).
- MESH :
- génétique : Endoribonucleases, Immunité, Protein-Serine-Threonine Kinases, Stress du réticulum endoplasmique, Survie cellulaire.
- immunologie : Activation des lymphocytes, Cellules tueuses naturelles, Interactions hôte-pathogène, Survie cellulaire.
- métabolisme : Cellules tueuses naturelles, Mitochondries, Protéine-1 liant la boite X.
- Animaux, Cytotoxicité immunologique, Gènes myc, Humains, Marqueurs biologiques, Mélanome expérimental, Phosphorylation oxydative, Régulation de l'expression des gènes, Souris, Souris knockout, Transduction du signal.
English descriptors
- KwdEn :
- Animals (MeSH), Biomarkers (MeSH), Cell Survival (genetics), Cell Survival (immunology), Cytotoxicity, Immunologic (MeSH), Endoplasmic Reticulum Stress (genetics), Endoribonucleases (genetics), Gene Expression Regulation (MeSH), Genes, myc (MeSH), Host-Pathogen Interactions (immunology), Humans (MeSH), Immunity (genetics), Killer Cells, Natural (immunology), Killer Cells, Natural (metabolism), Lymphocyte Activation (immunology), Melanoma, Experimental (MeSH), Mice (MeSH), Mice, Knockout (MeSH), Mitochondria (metabolism), Oxidative Phosphorylation (MeSH), Protein-Serine-Threonine Kinases (genetics), Signal Transduction (MeSH), X-Box Binding Protein 1 (metabolism).
- MESH :
- chemical , genetics : Endoribonucleases, Protein-Serine-Threonine Kinases.
- chemical , metabolism : X-Box Binding Protein 1.
- chemical : Biomarkers.
- genetics : Cell Survival, Endoplasmic Reticulum Stress, Immunity.
- immunology : Cell Survival, Host-Pathogen Interactions, Killer Cells, Natural, Lymphocyte Activation.
- metabolism : Killer Cells, Natural, Mitochondria.
- Animals, Cytotoxicity, Immunologic, Gene Expression Regulation, Genes, myc, Humans, Melanoma, Experimental, Mice, Mice, Knockout, Oxidative Phosphorylation, Signal Transduction.
Abstract
Natural killer (NK) cells are critical mediators of host immunity to pathogens. Here, we demonstrate that the endoplasmic reticulum stress sensor inositol-requiring enzyme 1 (IRE1α) and its substrate transcription factor X-box-binding protein 1 (XBP1) drive NK cell responses against viral infection and tumors in vivo. IRE1α-XBP1 were essential for expansion of activated mouse and human NK cells and are situated downstream of the mammalian target of rapamycin signaling pathway. Transcriptome and chromatin immunoprecipitation analysis revealed c-Myc as a new and direct downstream target of XBP1 for regulation of NK cell proliferation. Genetic ablation or pharmaceutical blockade of IRE1α downregulated c-Myc, and NK cells with c-Myc haploinsufficency phenocopied IRE1α-XBP1 deficiency. c-Myc overexpression largely rescued the proliferation defect in IRE1α-/- NK cells. Like c-Myc, IRE1α-XBP1 also promotes oxidative phosphorylation in NK cells. Overall, our study identifies a IRE1α-XBP1-cMyc axis in NK cell immunity, providing insight into host protection against infection and cancer.
DOI: 10.1038/s41590-019-0388-z
PubMed: 31086333
PubMed Central: PMC6588410
Affiliations:
- Canada, États-Unis
- Maryland, Massachusetts, Ontario, Texas, État de New York
- Toronto
- Université de Toronto
Links toward previous steps (curation, corpus...)
Le document en format XML
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Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Sun, Joseph C" sort="Sun, Joseph C" uniqKey="Sun J" first="Joseph C" last="Sun">Joseph C. Sun</name><affiliation wicri:level="2"><nlm:affiliation>Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Louis V. Gerstner, Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Louis V. Gerstner, Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Department of Immunology and Microbial Pathogenesis, Weill Cornell Medical College, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Immunology and Microbial Pathogenesis, Weill Cornell Medical College, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Glimcher, Laurie H" sort="Glimcher, Laurie H" uniqKey="Glimcher L" first="Laurie H" last="Glimcher">Laurie H. Glimcher</name><affiliation wicri:level="2"><nlm:affiliation>Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA. laurie_glimcher@dfci.harvard.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Department of Medicine Brigham and Women's Hospital, Boston, MA, USA. laurie_glimcher@dfci.harvard.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine Brigham and Women's Hospital, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, Harvard Medical School, Boston, MA, USA. laurie_glimcher@dfci.harvard.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Harvard Medical School, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2019">2019</date><idno type="RBID">pubmed:31086333</idno><idno type="pmid">31086333</idno><idno type="doi">10.1038/s41590-019-0388-z</idno><idno type="pmc">PMC6588410</idno><idno type="wicri:Area/Main/Corpus">000273</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000273</idno><idno type="wicri:Area/Main/Curation">000273</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000273</idno><idno type="wicri:Area/Main/Exploration">000273</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">The IRE1 endoplasmic reticulum stress sensor activates natural killer cell immunity in part by regulating c-Myc.</title><author><name sortKey="Dong, Han" sort="Dong, Han" uniqKey="Dong H" first="Han" last="Dong">Han Dong</name><affiliation wicri:level="2"><nlm:affiliation>Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Department of Medicine Brigham and Women's Hospital, Boston, MA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine Brigham and Women's Hospital, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, Harvard Medical School, Boston, MA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Harvard Medical School, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Adams, Nicholas M" sort="Adams, Nicholas M" uniqKey="Adams N" first="Nicholas M" last="Adams">Nicholas M. Adams</name><affiliation wicri:level="2"><nlm:affiliation>Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Louis V. Gerstner, Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Louis V. Gerstner, Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Xu, Yichi" sort="Xu, Yichi" uniqKey="Xu Y" first="Yichi" last="Xu">Yichi Xu</name><affiliation wicri:level="2"><nlm:affiliation>Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Cao, Jin" sort="Cao, Jin" uniqKey="Cao J" first="Jin" last="Cao">Jin Cao</name><affiliation wicri:level="2"><nlm:affiliation>Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Allan, David S J" sort="Allan, David S J" uniqKey="Allan D" first="David S J" last="Allan">David S J. Allan</name><affiliation wicri:level="2"><nlm:affiliation>National Heart Lung and Blood Institute, National Institute of Health, Bethesda, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>National Heart Lung and Blood Institute, National Institute of Health, Bethesda, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Carlyle, James R" sort="Carlyle, James R" uniqKey="Carlyle J" first="James R" last="Carlyle">James R. Carlyle</name><affiliation wicri:level="4"><nlm:affiliation>Department of Immunology, University of Toronto, Toronto, Onatario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Immunology, University of Toronto, Toronto, Onatario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation><affiliation wicri:level="1"><nlm:affiliation>Sunnybrook Research Institute, Toronto, Ontario, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Sunnybrook Research Institute, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Xi" sort="Chen, Xi" uniqKey="Chen X" first="Xi" last="Chen">Xi Chen</name><affiliation wicri:level="2"><nlm:affiliation>Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Sun, Joseph C" sort="Sun, Joseph C" uniqKey="Sun J" first="Joseph C" last="Sun">Joseph C. Sun</name><affiliation wicri:level="2"><nlm:affiliation>Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Louis V. Gerstner, Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Louis V. Gerstner, Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Department of Immunology and Microbial Pathogenesis, Weill Cornell Medical College, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Immunology and Microbial Pathogenesis, Weill Cornell Medical College, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Glimcher, Laurie H" sort="Glimcher, Laurie H" uniqKey="Glimcher L" first="Laurie H" last="Glimcher">Laurie H. Glimcher</name><affiliation wicri:level="2"><nlm:affiliation>Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA. laurie_glimcher@dfci.harvard.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Department of Medicine Brigham and Women's Hospital, Boston, MA, USA. laurie_glimcher@dfci.harvard.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine Brigham and Women's Hospital, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, Harvard Medical School, Boston, MA, USA. laurie_glimcher@dfci.harvard.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Harvard Medical School, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author></analytic><series><title level="j">Nature immunology</title><idno type="eISSN">1529-2916</idno><imprint><date when="2019" type="published">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals (MeSH)</term><term>Biomarkers (MeSH)</term><term>Cell Survival (genetics)</term><term>Cell Survival (immunology)</term><term>Cytotoxicity, Immunologic (MeSH)</term><term>Endoplasmic Reticulum Stress (genetics)</term><term>Endoribonucleases (genetics)</term><term>Gene Expression Regulation (MeSH)</term><term>Genes, myc (MeSH)</term><term>Host-Pathogen Interactions (immunology)</term><term>Humans (MeSH)</term><term>Immunity (genetics)</term><term>Killer Cells, Natural (immunology)</term><term>Killer Cells, Natural (metabolism)</term><term>Lymphocyte Activation (immunology)</term><term>Melanoma, Experimental (MeSH)</term><term>Mice (MeSH)</term><term>Mice, Knockout (MeSH)</term><term>Mitochondria (metabolism)</term><term>Oxidative Phosphorylation (MeSH)</term><term>Protein-Serine-Threonine Kinases (genetics)</term><term>Signal Transduction (MeSH)</term><term>X-Box Binding Protein 1 (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Activation des lymphocytes (immunologie)</term><term>Animaux (MeSH)</term><term>Cellules tueuses naturelles (immunologie)</term><term>Cellules tueuses naturelles (métabolisme)</term><term>Cytotoxicité immunologique (MeSH)</term><term>Endoribonucleases (génétique)</term><term>Gènes myc (MeSH)</term><term>Humains (MeSH)</term><term>Immunité (génétique)</term><term>Interactions hôte-pathogène (immunologie)</term><term>Marqueurs biologiques (MeSH)</term><term>Mitochondries (métabolisme)</term><term>Mélanome expérimental (MeSH)</term><term>Phosphorylation oxydative (MeSH)</term><term>Protein-Serine-Threonine Kinases (génétique)</term><term>Protéine-1 liant la boite X (métabolisme)</term><term>Régulation de l'expression des gènes (MeSH)</term><term>Souris (MeSH)</term><term>Souris knockout (MeSH)</term><term>Stress du réticulum endoplasmique (génétique)</term><term>Survie cellulaire (génétique)</term><term>Survie cellulaire (immunologie)</term><term>Transduction du signal (MeSH)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Endoribonucleases</term><term>Protein-Serine-Threonine Kinases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>X-Box Binding Protein 1</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Biomarkers</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Cell Survival</term><term>Endoplasmic Reticulum Stress</term><term>Immunity</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Endoribonucleases</term><term>Immunité</term><term>Protein-Serine-Threonine Kinases</term><term>Stress du réticulum endoplasmique</term><term>Survie cellulaire</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Activation des lymphocytes</term><term>Cellules tueuses naturelles</term><term>Interactions hôte-pathogène</term><term>Survie cellulaire</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Cell Survival</term><term>Host-Pathogen Interactions</term><term>Killer Cells, Natural</term><term>Lymphocyte Activation</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Killer Cells, Natural</term><term>Mitochondria</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Cellules tueuses naturelles</term><term>Mitochondries</term><term>Protéine-1 liant la boite X</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cytotoxicity, Immunologic</term><term>Gene Expression Regulation</term><term>Genes, myc</term><term>Humans</term><term>Melanoma, Experimental</term><term>Mice</term><term>Mice, Knockout</term><term>Oxidative Phosphorylation</term><term>Signal Transduction</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cytotoxicité immunologique</term><term>Gènes myc</term><term>Humains</term><term>Marqueurs biologiques</term><term>Mélanome expérimental</term><term>Phosphorylation oxydative</term><term>Régulation de l'expression des gènes</term><term>Souris</term><term>Souris knockout</term><term>Transduction du signal</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Natural killer (NK) cells are critical mediators of host immunity to pathogens. Here, we demonstrate that the endoplasmic reticulum stress sensor inositol-requiring enzyme 1 (IRE1α) and its substrate transcription factor X-box-binding protein 1 (XBP1) drive NK cell responses against viral infection and tumors in vivo. IRE1α-XBP1 were essential for expansion of activated mouse and human NK cells and are situated downstream of the mammalian target of rapamycin signaling pathway. Transcriptome and chromatin immunoprecipitation analysis revealed c-Myc as a new and direct downstream target of XBP1 for regulation of NK cell proliferation. Genetic ablation or pharmaceutical blockade of IRE1α downregulated c-Myc, and NK cells with c-Myc haploinsufficency phenocopied IRE1α-XBP1 deficiency. c-Myc overexpression largely rescued the proliferation defect in IRE1α<sup>-/-</sup> NK cells. Like c-Myc, IRE1α-XBP1 also promotes oxidative phosphorylation in NK cells. Overall, our study identifies a IRE1α-XBP1-cMyc axis in NK cell immunity, providing insight into host protection against infection and cancer.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">31086333</PMID><DateCompleted><Year>2019</Year><Month>07</Month><Day>09</Day></DateCompleted><DateRevised><Year>2020</Year><Month>06</Month><Day>17</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1529-2916</ISSN><JournalIssue CitedMedium="Internet"><Volume>20</Volume><Issue>7</Issue><PubDate><Year>2019</Year><Month>07</Month></PubDate></JournalIssue><Title>Nature immunology</Title><ISOAbbreviation>Nat Immunol</ISOAbbreviation></Journal><ArticleTitle>The IRE1 endoplasmic reticulum stress sensor activates natural killer cell immunity in part by regulating c-Myc.</ArticleTitle><Pagination><MedlinePgn>865-878</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/s41590-019-0388-z</ELocationID><Abstract><AbstractText>Natural killer (NK) cells are critical mediators of host immunity to pathogens. Here, we demonstrate that the endoplasmic reticulum stress sensor inositol-requiring enzyme 1 (IRE1α) and its substrate transcription factor X-box-binding protein 1 (XBP1) drive NK cell responses against viral infection and tumors in vivo. IRE1α-XBP1 were essential for expansion of activated mouse and human NK cells and are situated downstream of the mammalian target of rapamycin signaling pathway. Transcriptome and chromatin immunoprecipitation analysis revealed c-Myc as a new and direct downstream target of XBP1 for regulation of NK cell proliferation. Genetic ablation or pharmaceutical blockade of IRE1α downregulated c-Myc, and NK cells with c-Myc haploinsufficency phenocopied IRE1α-XBP1 deficiency. c-Myc overexpression largely rescued the proliferation defect in IRE1α<sup>-/-</sup> NK cells. Like c-Myc, IRE1α-XBP1 also promotes oxidative phosphorylation in NK cells. Overall, our study identifies a IRE1α-XBP1-cMyc axis in NK cell immunity, providing insight into host protection against infection and cancer.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Dong</LastName><ForeName>Han</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Medicine Brigham and Women's Hospital, Boston, MA, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, Harvard Medical School, Boston, MA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Adams</LastName><ForeName>Nicholas M</ForeName><Initials>NM</Initials><Identifier Source="ORCID">http://orcid.org/0000-0001-5751-0480</Identifier><AffiliationInfo><Affiliation>Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Louis V. Gerstner, Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xu</LastName><ForeName>Yichi</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cao</LastName><ForeName>Jin</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Allan</LastName><ForeName>David S J</ForeName><Initials>DSJ</Initials><AffiliationInfo><Affiliation>National Heart Lung and Blood Institute, National Institute of Health, Bethesda, MD, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Carlyle</LastName><ForeName>James R</ForeName><Initials>JR</Initials><AffiliationInfo><Affiliation>Department of Immunology, University of Toronto, Toronto, Onatario, Canada.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Sunnybrook Research Institute, Toronto, Ontario, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Xi</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sun</LastName><ForeName>Joseph C</ForeName><Initials>JC</Initials><Identifier Source="ORCID">http://orcid.org/0000-0001-8062-9033</Identifier><AffiliationInfo><Affiliation>Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Louis V. Gerstner, Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Immunology and Microbial Pathogenesis, Weill Cornell Medical College, New York, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Glimcher</LastName><ForeName>Laurie H</ForeName><Initials>LH</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-4971-0404</Identifier><AffiliationInfo><Affiliation>Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA. laurie_glimcher@dfci.harvard.edu.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Medicine Brigham and Women's Hospital, Boston, MA, USA. laurie_glimcher@dfci.harvard.edu.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, Harvard Medical School, Boston, MA, USA. laurie_glimcher@dfci.harvard.edu.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R01 AI100874</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R37 CA228304</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P30 CA008748</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R00 AI085034</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>T32 GM007739</GrantID><Acronym>GM</Acronym><Agency>NIGMS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>F30 AI136239</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P30 CA006516</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 AI130043</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>05</Month><Day>13</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Nat Immunol</MedlineTA><NlmUniqueID>100941354</NlmUniqueID><ISSNLinking>1529-2908</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D015415">Biomarkers</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000071717">X-Box Binding Protein 1</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C000605543">XBP1 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber><NameOfSubstance UI="C528229">ERN1 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber><NameOfSubstance UI="D017346">Protein-Serine-Threonine Kinases</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.1.-</RegistryNumber><NameOfSubstance UI="D004722">Endoribonucleases</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015415" MajorTopicYN="N">Biomarkers</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002470" MajorTopicYN="N">Cell Survival</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003602" MajorTopicYN="N">Cytotoxicity, Immunologic</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D059865" MajorTopicYN="N">Endoplasmic Reticulum Stress</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004722" MajorTopicYN="N">Endoribonucleases</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005786" MajorTopicYN="Y">Gene Expression Regulation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016259" MajorTopicYN="Y">Genes, myc</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D054884" MajorTopicYN="N">Host-Pathogen Interactions</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007109" MajorTopicYN="N">Immunity</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007694" MajorTopicYN="N">Killer Cells, Natural</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008213" MajorTopicYN="N">Lymphocyte Activation</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008546" MajorTopicYN="N">Melanoma, Experimental</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018345" MajorTopicYN="N">Mice, Knockout</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008928" MajorTopicYN="N">Mitochondria</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010085" MajorTopicYN="N">Oxidative Phosphorylation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017346" MajorTopicYN="N">Protein-Serine-Threonine Kinases</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015398" MajorTopicYN="N">Signal Transduction</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000071717" MajorTopicYN="N">X-Box Binding Protein 1</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2018</Year><Month>06</Month><Day>14</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2019</Year><Month>03</Month><Day>29</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>5</Month><Day>16</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2019</Year><Month>7</Month><Day>10</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>5</Month><Day>16</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">31086333</ArticleId><ArticleId IdType="doi">10.1038/s41590-019-0388-z</ArticleId><ArticleId IdType="pii">10.1038/s41590-019-0388-z</ArticleId><ArticleId IdType="pmc">PMC6588410</ArticleId><ArticleId IdType="mid">NIHMS1525854</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Canada</li><li>États-Unis</li></country><region><li>Maryland</li><li>Massachusetts</li><li>Ontario</li><li>Texas</li><li>État de New York</li></region><settlement><li>Toronto</li></settlement><orgName><li>Université de Toronto</li></orgName></list><tree><country name="États-Unis"><region name="Massachusetts"><name sortKey="Dong, Han" sort="Dong, Han" uniqKey="Dong H" first="Han" last="Dong">Han Dong</name></region><name sortKey="Adams, Nicholas M" sort="Adams, Nicholas M" uniqKey="Adams N" first="Nicholas M" last="Adams">Nicholas M. Adams</name><name sortKey="Adams, Nicholas M" sort="Adams, Nicholas M" uniqKey="Adams N" first="Nicholas M" last="Adams">Nicholas M. Adams</name><name sortKey="Allan, David S J" sort="Allan, David S J" uniqKey="Allan D" first="David S J" last="Allan">David S J. Allan</name><name sortKey="Cao, Jin" sort="Cao, Jin" uniqKey="Cao J" first="Jin" last="Cao">Jin Cao</name><name sortKey="Cao, Jin" sort="Cao, Jin" uniqKey="Cao J" first="Jin" last="Cao">Jin Cao</name><name sortKey="Cao, Jin" sort="Cao, Jin" uniqKey="Cao J" first="Jin" last="Cao">Jin Cao</name><name sortKey="Chen, Xi" sort="Chen, Xi" uniqKey="Chen X" first="Xi" last="Chen">Xi Chen</name><name sortKey="Chen, Xi" sort="Chen, Xi" uniqKey="Chen X" first="Xi" last="Chen">Xi Chen</name><name sortKey="Chen, Xi" sort="Chen, Xi" uniqKey="Chen X" first="Xi" last="Chen">Xi Chen</name><name sortKey="Dong, Han" sort="Dong, Han" uniqKey="Dong H" first="Han" last="Dong">Han Dong</name><name sortKey="Dong, Han" sort="Dong, Han" uniqKey="Dong H" first="Han" last="Dong">Han Dong</name><name sortKey="Glimcher, Laurie H" sort="Glimcher, Laurie H" uniqKey="Glimcher L" first="Laurie H" last="Glimcher">Laurie H. Glimcher</name><name sortKey="Glimcher, Laurie H" sort="Glimcher, Laurie H" uniqKey="Glimcher L" first="Laurie H" last="Glimcher">Laurie H. Glimcher</name><name sortKey="Glimcher, Laurie H" sort="Glimcher, Laurie H" uniqKey="Glimcher L" first="Laurie H" last="Glimcher">Laurie H. Glimcher</name><name sortKey="Sun, Joseph C" sort="Sun, Joseph C" uniqKey="Sun J" first="Joseph C" last="Sun">Joseph C. Sun</name><name sortKey="Sun, Joseph C" sort="Sun, Joseph C" uniqKey="Sun J" first="Joseph C" last="Sun">Joseph C. Sun</name><name sortKey="Sun, Joseph C" sort="Sun, Joseph C" uniqKey="Sun J" first="Joseph C" last="Sun">Joseph C. Sun</name><name sortKey="Xu, Yichi" sort="Xu, Yichi" uniqKey="Xu Y" first="Yichi" last="Xu">Yichi Xu</name></country><country name="Canada"><region name="Ontario"><name sortKey="Carlyle, James R" sort="Carlyle, James R" uniqKey="Carlyle J" first="James R" last="Carlyle">James R. Carlyle</name></region><name sortKey="Carlyle, James R" sort="Carlyle, James R" uniqKey="Carlyle J" first="James R" last="Carlyle">James R. Carlyle</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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