A pro‐survival role for the intracellular granzyme B inhibitor Serpinb9 in natural killer cells during poxvirus infection
Intracellular serpins are proposed to inactivate proteases released from lysosome‐related organelles into the host cell interior, preventing cell death. Serpinb9 opposes the immune cytotoxic protease, granzyme B, and in a number of settings protects cells against granzyme B‐mediated cell death. Usin...
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| Veröffentlicht in: | Immunology and cell biology 2017-11, Vol.95 (10), p.884-894 |
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| creator | Mangan, Matthew S Melo‐Silva, Carolina R Luu, Jennii Bird, Catherina H Koskinen, Aulikki Rizzitelli, Alexandra Prakash, Monica Scarff, Katrina L Müllbacher, Arno Regner, Matthias Bird, Phillip I |
| description | Intracellular serpins are proposed to inactivate proteases released from lysosome‐related organelles into the host cell interior, preventing cell death. Serpinb9 opposes the immune cytotoxic protease, granzyme B, and in a number of settings protects cells against granzyme B‐mediated cell death. Using a knockout mouse line engineered to express green fluorescent protein under the serpbinb9 promoter, we demonstrate that serpinb9 is vital for host survival during Ectromelia virus infection by maintaining both mature natural killer NK) cells, and activated CD8+ T cells. Serpinb9 expression parallels granzyme B expression within both populations during infection. Maturing serpinb9‐null NK cells exhibit higher levels of granzyme B‐mediated apoptosis during infection; hence there are fewer mature NK cells, and these cells also have lower cytotoxic potential. Thus the serpinb9–granzyme B axis is important for homeostasis of both major cytotoxic effector cell populations. |
| doi_str_mv | 10.1038/icb.2017.59 |
| format | Article |
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Serpinb9 opposes the immune cytotoxic protease, granzyme B, and in a number of settings protects cells against granzyme B‐mediated cell death. Using a knockout mouse line engineered to express green fluorescent protein under the serpbinb9 promoter, we demonstrate that serpinb9 is vital for host survival during Ectromelia virus infection by maintaining both mature natural killer NK) cells, and activated CD8+ T cells. Serpinb9 expression parallels granzyme B expression within both populations during infection. Maturing serpinb9‐null NK cells exhibit higher levels of granzyme B‐mediated apoptosis during infection; hence there are fewer mature NK cells, and these cells also have lower cytotoxic potential. Thus the serpinb9–granzyme B axis is important for homeostasis of both major cytotoxic effector cell populations.</description><identifier>ISSN: 0818-9641</identifier><identifier>EISSN: 1440-1711</identifier><identifier>DOI: 10.1038/icb.2017.59</identifier><identifier>PMID: 28722018</identifier><language>eng</language><publisher>England: Nature Publishing Group</publisher><subject>Animals ; Apoptosis ; CD8 antigen ; Cell Death ; Cell Survival ; Cytotoxicity ; Granzyme B ; Granzymes - antagonists & inhibitors ; Green fluorescent protein ; Homeostasis ; Humans ; Infections ; Intracellular ; Intracellular Space ; Killer Cells, Natural - immunology ; Lymphocytes B ; Lymphocytes T ; Membrane Proteins - pharmacology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Natural killer cells ; Organelles ; Poxviridae - immunology ; Poxviridae Infections - immunology ; Serine proteinase inhibitors ; Serpins - pharmacology</subject><ispartof>Immunology and cell biology, 2017-11, Vol.95 (10), p.884-894</ispartof><rights>2017 Australasian Society for Immunology Inc.</rights><rights>Copyright Nature Publishing Group Nov 2017</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3619-60def7542d60a8863c8e6ad7966fbc77e9ecb1dc1a12ac00f87735584f39376d3</citedby><cites>FETCH-LOGICAL-c3619-60def7542d60a8863c8e6ad7966fbc77e9ecb1dc1a12ac00f87735584f39376d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1038%2Ficb.2017.59$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1038%2Ficb.2017.59$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28722018$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mangan, Matthew S</creatorcontrib><creatorcontrib>Melo‐Silva, Carolina R</creatorcontrib><creatorcontrib>Luu, Jennii</creatorcontrib><creatorcontrib>Bird, Catherina H</creatorcontrib><creatorcontrib>Koskinen, Aulikki</creatorcontrib><creatorcontrib>Rizzitelli, Alexandra</creatorcontrib><creatorcontrib>Prakash, Monica</creatorcontrib><creatorcontrib>Scarff, Katrina L</creatorcontrib><creatorcontrib>Müllbacher, Arno</creatorcontrib><creatorcontrib>Regner, Matthias</creatorcontrib><creatorcontrib>Bird, Phillip I</creatorcontrib><title>A pro‐survival role for the intracellular granzyme B inhibitor Serpinb9 in natural killer cells during poxvirus infection</title><title>Immunology and cell biology</title><addtitle>Immunol Cell Biol</addtitle><description>Intracellular serpins are proposed to inactivate proteases released from lysosome‐related organelles into the host cell interior, preventing cell death. Serpinb9 opposes the immune cytotoxic protease, granzyme B, and in a number of settings protects cells against granzyme B‐mediated cell death. Using a knockout mouse line engineered to express green fluorescent protein under the serpbinb9 promoter, we demonstrate that serpinb9 is vital for host survival during Ectromelia virus infection by maintaining both mature natural killer NK) cells, and activated CD8+ T cells. Serpinb9 expression parallels granzyme B expression within both populations during infection. Maturing serpinb9‐null NK cells exhibit higher levels of granzyme B‐mediated apoptosis during infection; hence there are fewer mature NK cells, and these cells also have lower cytotoxic potential. Thus the serpinb9–granzyme B axis is important for homeostasis of both major cytotoxic effector cell populations.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>CD8 antigen</subject><subject>Cell Death</subject><subject>Cell Survival</subject><subject>Cytotoxicity</subject><subject>Granzyme B</subject><subject>Granzymes - antagonists & inhibitors</subject><subject>Green fluorescent protein</subject><subject>Homeostasis</subject><subject>Humans</subject><subject>Infections</subject><subject>Intracellular</subject><subject>Intracellular Space</subject><subject>Killer Cells, Natural - immunology</subject><subject>Lymphocytes B</subject><subject>Lymphocytes T</subject><subject>Membrane Proteins - pharmacology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Natural killer cells</subject><subject>Organelles</subject><subject>Poxviridae - immunology</subject><subject>Poxviridae Infections - immunology</subject><subject>Serine proteinase inhibitors</subject><subject>Serpins - pharmacology</subject><issn>0818-9641</issn><issn>1440-1711</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp90ctu1DAUBmALgehQWLFHltggoQw-ceLLsh1xqVTEAlhbjuO0Lp5kOI4HBjY8As_Ik-BoCgsWrGzZn38d6yfkMbA1MK5eBNetawZy3eo7ZAVNwyqQAHfJiilQlRYNnJAHKd0wxmSt-H1yUitZlydqRb6f0R1Ov378TBn3YW8jxSl6OkxI52tPwzijdT7GHC3SK7Tjt8PW0_NycR26MBf23uMujJ0uR3S0c8aS8SnE6JEuDxPtM4bxiu6mr_uAORU3eDeHaXxI7g02Jv_odj0lH1-9_LB5U12-e32xObusHBegK8F6P8i2qXvBrFKCO-WF7aUWYuiclF5710HvwEJtHWODkpK3rWoGrrkUPT8lz4655aefs0-z2Ya0zGZHP-VkQNeM60YoWejTf-jNlHEs0xUlRMMaqKGo50flcEoJ_WB2GLYWDwaYWToxpROzdGJaXfST28zcbX3_1_4poQB-BF9C9If_ZZmLt5vzZV9ifwNUyJki</recordid><startdate>201711</startdate><enddate>201711</enddate><creator>Mangan, Matthew S</creator><creator>Melo‐Silva, Carolina R</creator><creator>Luu, Jennii</creator><creator>Bird, Catherina H</creator><creator>Koskinen, Aulikki</creator><creator>Rizzitelli, Alexandra</creator><creator>Prakash, Monica</creator><creator>Scarff, Katrina L</creator><creator>Müllbacher, Arno</creator><creator>Regner, Matthias</creator><creator>Bird, Phillip I</creator><general>Nature Publishing Group</general><general>Blackwell Science Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>201711</creationdate><title>A pro‐survival role for the intracellular granzyme B inhibitor Serpinb9 in natural killer cells during poxvirus infection</title><author>Mangan, Matthew S ; 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Serpinb9 opposes the immune cytotoxic protease, granzyme B, and in a number of settings protects cells against granzyme B‐mediated cell death. Using a knockout mouse line engineered to express green fluorescent protein under the serpbinb9 promoter, we demonstrate that serpinb9 is vital for host survival during Ectromelia virus infection by maintaining both mature natural killer NK) cells, and activated CD8+ T cells. Serpinb9 expression parallels granzyme B expression within both populations during infection. Maturing serpinb9‐null NK cells exhibit higher levels of granzyme B‐mediated apoptosis during infection; hence there are fewer mature NK cells, and these cells also have lower cytotoxic potential. Thus the serpinb9–granzyme B axis is important for homeostasis of both major cytotoxic effector cell populations.</abstract><cop>England</cop><pub>Nature Publishing Group</pub><pmid>28722018</pmid><doi>10.1038/icb.2017.59</doi><tpages>11</tpages></addata></record> |
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| subjects | Animals Apoptosis CD8 antigen Cell Death Cell Survival Cytotoxicity Granzyme B Granzymes - antagonists & inhibitors Green fluorescent protein Homeostasis Humans Infections Intracellular Intracellular Space Killer Cells, Natural - immunology Lymphocytes B Lymphocytes T Membrane Proteins - pharmacology Mice Mice, Inbred C57BL Mice, Knockout Natural killer cells Organelles Poxviridae - immunology Poxviridae Infections - immunology Serine proteinase inhibitors Serpins - pharmacology |
| title | A pro‐survival role for the intracellular granzyme B inhibitor Serpinb9 in natural killer cells during poxvirus infection |
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