Interleukin 15mediated survival of natural killer cells is determined by interactions among Bim, Noxa and Mcl-1
Identifieur interne : 009139 ( Main/Exploration ); précédent : 009138; suivant : 009140Interleukin 15mediated survival of natural killer cells is determined by interactions among Bim, Noxa and Mcl-1
Auteurs : Nicholas D. Huntington [Australie, France] ; Hamsa Puthalakath [Australie] ; Priscilla Gunn [Australie] ; Edwina Naik [Australie] ; Ewa M. Michalak [Australie] ; Mark J. Smyth [Australie] ; Hyacinth Tabarias [Australie] ; Mariapia A. Degli-Esposti [Australie] ; Grant Dewson [Australie] ; Simon N. Willis [Australie] ; Noboru Motoyama [Japon] ; David C S. Huang [Australie] ; Stephen L. Nutt [Australie] ; David M. Tarlinton [Australie] ; Andreas Strasser [Australie]Source :
- Nature Immunology [ 1529-2908 ] ; 2007-08.
Descripteurs français
- Wicri :
- topic : Immunologie, Recherche médicale.
English descriptors
- KwdEn :
- Abbot laboratories, Abnormal accumulation, Antigen receptors, Apoptosis, Apoptotic stimuli, August, Bimel, Bimel biml, Bone marrow, Cell, Cell apoptosis, Cell death, Cell function, Cell maturation, Cell numbers, Cell populations, Cell proliferation, Cell survival, Control mice, Cultured, Cytokine, Cytokine deprivation, Cytometry, Dead cells, Deprivation, Dimethyl sulfoxide, Eliza hall, Eliza hall institute, Equal numbers, Family member, Flow cytometry, Foxo3a, Foxo3a activity, Hematopoietic cells, Homeostasis, Horizontal axis, Immunoblot, Immunoblot analysis, Immunol, Immunology, Inactivating mutation, Independent experiments, Inhibitor, Killer cells, Kinase, Kinases erk1, Klrg1, Klrg1 expression, Lesser extent, Loading control, Lymphocyte, Maccallum cancer centre, Major histocompatibility, Mcmv, Mcmv infection, Medical research, Medical research council, Mouse, Myeloid cells, National health, Natural killer, Natural killer cells, Nature immunology, Nature immunology volume, Nature publishing group, Nature publishing group articles, Nding, Normal numbers, Noxa, Noxa acts, Noxa expression, Pathway, Percent cells, Peripheral homeostasis, Phosphorylated, Phosphorylated foxo3a, Phosphorylation, Proapoptotic, Proapoptotic effects, Proapoptotic family member, Prosurvival proteins, Proteasomal degradation, Proteasome inhibitor, Protein kinase, Puma, Receptor, Recipient mice, Spleen, Statistical analysis, Total foxo3a, Total number, Transcription, Transcription factor foxo3a, Transcriptional induction, Unpublished data, Untreated cells, Uorescence intensity, Various times, Viability.
- Teeft :
- Abbot laboratories, Abnormal accumulation, Antigen receptors, Apoptosis, Apoptotic stimuli, August, Bimel, Bimel biml, Bone marrow, Cell, Cell apoptosis, Cell death, Cell function, Cell maturation, Cell numbers, Cell populations, Cell proliferation, Cell survival, Control mice, Cultured, Cytokine, Cytokine deprivation, Cytometry, Dead cells, Deprivation, Dimethyl sulfoxide, Eliza hall, Eliza hall institute, Equal numbers, Family member, Flow cytometry, Foxo3a, Foxo3a activity, Hematopoietic cells, Homeostasis, Horizontal axis, Immunoblot, Immunoblot analysis, Immunol, Immunology, Inactivating mutation, Independent experiments, Inhibitor, Killer cells, Kinase, Kinases erk1, Klrg1, Klrg1 expression, Lesser extent, Loading control, Lymphocyte, Maccallum cancer centre, Major histocompatibility, Mcmv, Mcmv infection, Medical research, Medical research council, Mouse, Myeloid cells, National health, Natural killer, Natural killer cells, Nature immunology, Nature immunology volume, Nature publishing group, Nature publishing group articles, Nding, Normal numbers, Noxa, Noxa acts, Noxa expression, Pathway, Percent cells, Peripheral homeostasis, Phosphorylated, Phosphorylated foxo3a, Phosphorylation, Proapoptotic, Proapoptotic effects, Proapoptotic family member, Prosurvival proteins, Proteasomal degradation, Proteasome inhibitor, Protein kinase, Puma, Receptor, Recipient mice, Spleen, Statistical analysis, Total foxo3a, Total number, Transcription, Transcription factor foxo3a, Transcriptional induction, Unpublished data, Untreated cells, Uorescence intensity, Various times, Viability.
Abstract
Interleukin 15 (IL-15) promotes the survival of natural killer (NK) cells by preventing apoptosis through mechanisms unknown at present. Here we identify Bim, Noxa and Mcl-1 as key regulators of IL-15-dependent survival of NK cells. IL-15 suppressed apoptosis by limiting Bim expression through the kinases Erk1 and Erk2 and mechanisms dependent on the transcription factor Foxo3a, while promoting expression of Mcl-1, which was necessary and sufficient for the survival of NK cells. Withdrawal of IL-15 led to upregulation of Bim and, accordingly, both Bim-deficient and Foxo3a/ NK cells were resistant to cytokine deprivation. Finally, IL-15-mediated inactivation of Foxo3a and cell survival were dependent on phosphotidylinositol-3-OH kinase. Thus, IL-15 regulates the survival of NK cells at multiple steps, with Bim and Noxa being key antagonists of Mcl-1, the critical survivor factor in this process.
Url:
DOI: 10.1038/ni1487
Affiliations:
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Willis</name><affiliation wicri:level="1"><country xml:lang="fr" wicri:curation="lc">Australie</country><wicri:regionArea>The Walter and Eliza Hall Institute of Medical Research, Parkville</wicri:regionArea><wicri:noRegion>Parkville</wicri:noRegion></affiliation></author><author><name sortKey="Motoyama, Noboru" sort="Motoyama, Noboru" uniqKey="Motoyama N" first="Noboru" last="Motoyama">Noboru Motoyama</name><affiliation wicri:level="1"><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Geriatric Medicine, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Aichi 474-8522</wicri:regionArea><wicri:noRegion>Aichi 474-8522</wicri:noRegion></affiliation></author><author><name sortKey="Huang, David C S" sort="Huang, David C S" uniqKey="Huang D" first="David C S" last="Huang">David C S. Huang</name><affiliation wicri:level="1"><country xml:lang="fr" wicri:curation="lc">Australie</country><wicri:regionArea>The Walter and Eliza Hall Institute of Medical Research, Parkville</wicri:regionArea><wicri:noRegion>Parkville</wicri:noRegion></affiliation></author><author><name sortKey="Nutt, Stephen L" sort="Nutt, Stephen L" uniqKey="Nutt S" first="Stephen L" last="Nutt">Stephen L. Nutt</name><affiliation wicri:level="1"><country xml:lang="fr" wicri:curation="lc">Australie</country><wicri:regionArea>The Walter and Eliza Hall Institute of Medical Research, Parkville</wicri:regionArea><wicri:noRegion>Parkville</wicri:noRegion></affiliation><affiliation></affiliation></author><author><name sortKey="Tarlinton, David M" sort="Tarlinton, David M" uniqKey="Tarlinton D" first="David M" last="Tarlinton">David M. Tarlinton</name><affiliation wicri:level="1"><country xml:lang="fr" wicri:curation="lc">Australie</country><wicri:regionArea>The Walter and Eliza Hall Institute of Medical Research, Parkville</wicri:regionArea><wicri:noRegion>Parkville</wicri:noRegion></affiliation><affiliation></affiliation></author><author><name sortKey="Strasser, Andreas" sort="Strasser, Andreas" uniqKey="Strasser A" first="Andreas" last="Strasser">Andreas Strasser</name><affiliation wicri:level="1"><country xml:lang="fr" wicri:curation="lc">Australie</country><wicri:regionArea>The Walter and Eliza Hall Institute of Medical Research, Parkville</wicri:regionArea><wicri:noRegion>Parkville</wicri:noRegion></affiliation><affiliation></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Australie</country></affiliation></author></analytic><monogr></monogr><series><title level="j">Nature Immunology</title><idno type="ISSN">1529-2908</idno><imprint><publisher>Nature Publishing Group</publisher><date type="published" when="2007-08">2007-08</date><biblScope unit="volume">8</biblScope><biblScope unit="issue">8</biblScope><biblScope unit="page" from="856">856</biblScope><biblScope unit="page" to="863">863</biblScope></imprint><idno type="ISSN">1529-2908</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1529-2908</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Abbot laboratories</term><term>Abnormal accumulation</term><term>Antigen receptors</term><term>Apoptosis</term><term>Apoptotic stimuli</term><term>August</term><term>Bimel</term><term>Bimel biml</term><term>Bone marrow</term><term>Cell</term><term>Cell apoptosis</term><term>Cell death</term><term>Cell function</term><term>Cell maturation</term><term>Cell numbers</term><term>Cell populations</term><term>Cell proliferation</term><term>Cell survival</term><term>Control mice</term><term>Cultured</term><term>Cytokine</term><term>Cytokine deprivation</term><term>Cytometry</term><term>Dead cells</term><term>Deprivation</term><term>Dimethyl sulfoxide</term><term>Eliza hall</term><term>Eliza hall institute</term><term>Equal numbers</term><term>Family member</term><term>Flow cytometry</term><term>Foxo3a</term><term>Foxo3a activity</term><term>Hematopoietic cells</term><term>Homeostasis</term><term>Horizontal axis</term><term>Immunoblot</term><term>Immunoblot analysis</term><term>Immunol</term><term>Immunology</term><term>Inactivating mutation</term><term>Independent experiments</term><term>Inhibitor</term><term>Killer cells</term><term>Kinase</term><term>Kinases erk1</term><term>Klrg1</term><term>Klrg1 expression</term><term>Lesser extent</term><term>Loading control</term><term>Lymphocyte</term><term>Maccallum cancer centre</term><term>Major histocompatibility</term><term>Mcmv</term><term>Mcmv infection</term><term>Medical research</term><term>Medical research council</term><term>Mouse</term><term>Myeloid cells</term><term>National health</term><term>Natural killer</term><term>Natural killer cells</term><term>Nature immunology</term><term>Nature immunology volume</term><term>Nature publishing group</term><term>Nature publishing group articles</term><term>Nding</term><term>Normal numbers</term><term>Noxa</term><term>Noxa acts</term><term>Noxa expression</term><term>Pathway</term><term>Percent cells</term><term>Peripheral homeostasis</term><term>Phosphorylated</term><term>Phosphorylated foxo3a</term><term>Phosphorylation</term><term>Proapoptotic</term><term>Proapoptotic effects</term><term>Proapoptotic family member</term><term>Prosurvival proteins</term><term>Proteasomal degradation</term><term>Proteasome inhibitor</term><term>Protein kinase</term><term>Puma</term><term>Receptor</term><term>Recipient mice</term><term>Spleen</term><term>Statistical analysis</term><term>Total foxo3a</term><term>Total number</term><term>Transcription</term><term>Transcription factor foxo3a</term><term>Transcriptional induction</term><term>Unpublished data</term><term>Untreated cells</term><term>Uorescence intensity</term><term>Various times</term><term>Viability</term></keywords><keywords scheme="Teeft" xml:lang="en"><term>Abbot laboratories</term><term>Abnormal accumulation</term><term>Antigen receptors</term><term>Apoptosis</term><term>Apoptotic stimuli</term><term>August</term><term>Bimel</term><term>Bimel biml</term><term>Bone marrow</term><term>Cell</term><term>Cell apoptosis</term><term>Cell death</term><term>Cell function</term><term>Cell maturation</term><term>Cell numbers</term><term>Cell populations</term><term>Cell proliferation</term><term>Cell survival</term><term>Control mice</term><term>Cultured</term><term>Cytokine</term><term>Cytokine deprivation</term><term>Cytometry</term><term>Dead cells</term><term>Deprivation</term><term>Dimethyl sulfoxide</term><term>Eliza hall</term><term>Eliza hall institute</term><term>Equal numbers</term><term>Family member</term><term>Flow cytometry</term><term>Foxo3a</term><term>Foxo3a activity</term><term>Hematopoietic cells</term><term>Homeostasis</term><term>Horizontal axis</term><term>Immunoblot</term><term>Immunoblot analysis</term><term>Immunol</term><term>Immunology</term><term>Inactivating mutation</term><term>Independent experiments</term><term>Inhibitor</term><term>Killer cells</term><term>Kinase</term><term>Kinases erk1</term><term>Klrg1</term><term>Klrg1 expression</term><term>Lesser extent</term><term>Loading control</term><term>Lymphocyte</term><term>Maccallum cancer centre</term><term>Major histocompatibility</term><term>Mcmv</term><term>Mcmv infection</term><term>Medical research</term><term>Medical research council</term><term>Mouse</term><term>Myeloid cells</term><term>National health</term><term>Natural killer</term><term>Natural killer cells</term><term>Nature immunology</term><term>Nature immunology volume</term><term>Nature publishing group</term><term>Nature publishing group articles</term><term>Nding</term><term>Normal numbers</term><term>Noxa</term><term>Noxa acts</term><term>Noxa expression</term><term>Pathway</term><term>Percent cells</term><term>Peripheral homeostasis</term><term>Phosphorylated</term><term>Phosphorylated foxo3a</term><term>Phosphorylation</term><term>Proapoptotic</term><term>Proapoptotic effects</term><term>Proapoptotic family member</term><term>Prosurvival proteins</term><term>Proteasomal degradation</term><term>Proteasome inhibitor</term><term>Protein kinase</term><term>Puma</term><term>Receptor</term><term>Recipient mice</term><term>Spleen</term><term>Statistical analysis</term><term>Total foxo3a</term><term>Total number</term><term>Transcription</term><term>Transcription factor foxo3a</term><term>Transcriptional induction</term><term>Unpublished data</term><term>Untreated cells</term><term>Uorescence intensity</term><term>Various times</term><term>Viability</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Immunologie</term><term>Recherche médicale</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="eng">Interleukin 15 (IL-15) promotes the survival of natural killer (NK) cells by preventing apoptosis through mechanisms unknown at present. Here we identify Bim, Noxa and Mcl-1 as key regulators of IL-15-dependent survival of NK cells. IL-15 suppressed apoptosis by limiting Bim expression through the kinases Erk1 and Erk2 and mechanisms dependent on the transcription factor Foxo3a, while promoting expression of Mcl-1, which was necessary and sufficient for the survival of NK cells. Withdrawal of IL-15 led to upregulation of Bim and, accordingly, both Bim-deficient and Foxo3a/ NK cells were resistant to cytokine deprivation. Finally, IL-15-mediated inactivation of Foxo3a and cell survival were dependent on phosphotidylinositol-3-OH kinase. Thus, IL-15 regulates the survival of NK cells at multiple steps, with Bim and Noxa being key antagonists of Mcl-1, the critical survivor factor in this process.</div></front></TEI><affiliations><list><country><li>Australie</li><li>France</li><li>Japon</li></country><region><li>Victoria (État)</li><li>Île-de-France</li></region><settlement><li>Melbourne</li></settlement><orgName><li>Université de Melbourne</li></orgName></list><tree><country name="Australie"><noRegion><name sortKey="Huntington, Nicholas D" sort="Huntington, Nicholas D" uniqKey="Huntington N" first="Nicholas D" last="Huntington">Nicholas D. Huntington</name></noRegion><name sortKey="Degli Esposti, Mariapia A" sort="Degli Esposti, Mariapia A" uniqKey="Degli Esposti M" first="Mariapia A" last="Degli-Esposti">Mariapia A. Degli-Esposti</name><name sortKey="Dewson, Grant" sort="Dewson, Grant" uniqKey="Dewson G" first="Grant" last="Dewson">Grant Dewson</name><name sortKey="Gunn, Priscilla" sort="Gunn, Priscilla" uniqKey="Gunn P" first="Priscilla" last="Gunn">Priscilla Gunn</name><name sortKey="Huang, David C S" sort="Huang, David C S" uniqKey="Huang D" first="David C S" last="Huang">David C S. Huang</name><name sortKey="Huntington, Nicholas D" sort="Huntington, Nicholas D" uniqKey="Huntington N" first="Nicholas D" last="Huntington">Nicholas D. Huntington</name><name sortKey="Michalak, Ewa M" sort="Michalak, Ewa M" uniqKey="Michalak E" first="Ewa M" last="Michalak">Ewa M. Michalak</name><name sortKey="Michalak, Ewa M" sort="Michalak, Ewa M" uniqKey="Michalak E" first="Ewa M" last="Michalak">Ewa M. Michalak</name><name sortKey="Naik, Edwina" sort="Naik, Edwina" uniqKey="Naik E" first="Edwina" last="Naik">Edwina Naik</name><name sortKey="Naik, Edwina" sort="Naik, Edwina" uniqKey="Naik E" first="Edwina" last="Naik">Edwina Naik</name><name sortKey="Nutt, Stephen L" sort="Nutt, Stephen L" uniqKey="Nutt S" first="Stephen L" last="Nutt">Stephen L. Nutt</name><name sortKey="Puthalakath, Hamsa" sort="Puthalakath, Hamsa" uniqKey="Puthalakath H" first="Hamsa" last="Puthalakath">Hamsa Puthalakath</name><name sortKey="Smyth, Mark J" sort="Smyth, Mark J" uniqKey="Smyth M" first="Mark J" last="Smyth">Mark J. Smyth</name><name sortKey="Strasser, Andreas" sort="Strasser, Andreas" uniqKey="Strasser A" first="Andreas" last="Strasser">Andreas Strasser</name><name sortKey="Strasser, Andreas" sort="Strasser, Andreas" uniqKey="Strasser A" first="Andreas" last="Strasser">Andreas Strasser</name><name sortKey="Tabarias, Hyacinth" sort="Tabarias, Hyacinth" uniqKey="Tabarias H" first="Hyacinth" last="Tabarias">Hyacinth Tabarias</name><name sortKey="Tarlinton, David M" sort="Tarlinton, David M" uniqKey="Tarlinton D" first="David M" last="Tarlinton">David M. Tarlinton</name><name sortKey="Willis, Simon N" sort="Willis, Simon N" uniqKey="Willis S" first="Simon N" last="Willis">Simon N. Willis</name></country><country name="France"><region name="Île-de-France"><name sortKey="Huntington, Nicholas D" sort="Huntington, Nicholas D" uniqKey="Huntington N" first="Nicholas D" last="Huntington">Nicholas D. Huntington</name></region><name sortKey="Huntington, Nicholas D" sort="Huntington, Nicholas D" uniqKey="Huntington N" first="Nicholas D" last="Huntington">Nicholas D. Huntington</name></country><country name="Japon"><noRegion><name sortKey="Motoyama, Noboru" sort="Motoyama, Noboru" uniqKey="Motoyama N" first="Noboru" last="Motoyama">Noboru Motoyama</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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