IL‐27 stimulates human NK‐cell effector functions and primes NK cells for IL‐18 responsiveness
IL‐27, a member of the IL‐12 family of cytokines, is produced by APCs, and displays pro‐ and anti‐inflammatory effects. How IL‐27 affects human NK cells still remains unknown. In this study, we observed that mature DCs secreted IL‐27 and that blockade of IL‐27R (CD130) reduced the amount of IFN‐γ pr...
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| Veröffentlicht in: | European journal of immunology 2015-01, Vol.45 (1), p.192-202 |
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| creator | Ziblat, Andrea Domaica, Carolina I. Spallanzani, Raúl G. Iraolagoitia, Ximena L. Raffo Rossi, Lucas E. Avila, Damián E. Torres, Nicolás I. Fuertes, Mercedes B. Zwirner, Norberto W. |
| description | IL‐27, a member of the IL‐12 family of cytokines, is produced by APCs, and displays pro‐ and anti‐inflammatory effects. How IL‐27 affects human NK cells still remains unknown. In this study, we observed that mature DCs secreted IL‐27 and that blockade of IL‐27R (CD130) reduced the amount of IFN‐γ produced by NK cells during their coculture, showing the importance of IL‐27 during DC–NK‐cell crosstalk. Accordingly, human rIL‐27 stimulated IFN‐γ secretion by NK cells in a STAT1‐dependent manner, induced upregulation of CD25 and CD69 on NK cells, and displayed a synergistic effect with IL‐18. Preincubation experiments demonstrated that IL‐27 primed NK cells for IL‐18‐induced IFN‐γ secretion, which was associated with an IL‐27‐driven upregulation of T‐bet expression. Also, IL‐27 triggered NKp46‐dependent NK‐cell‐mediated cytotoxicity against Raji, T‐47D, and HCT116 cells, and IL‐18 enhanced this cytotoxic response. Such NK‐cell‐mediated cytotoxicity involved upregulation of perforin, granule exocytosis, and TRAIL‐mediated cytotoxicity but not Fas‐FasL interaction. Moreover, IL‐27 also potentiated Ab‐dependent cell‐mediated cytotoxicity against mAb‐coated target cells. Taken together, IL‐27 stimulates NK‐cell effector functions, which might be relevant in different physiological and pathological situations. |
| doi_str_mv | 10.1002/eji.201444699 |
| format | Article |
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Raffo ; Rossi, Lucas E. ; Avila, Damián E. ; Torres, Nicolás I. ; Fuertes, Mercedes B. ; Zwirner, Norberto W.</creator><creatorcontrib>Ziblat, Andrea ; Domaica, Carolina I. ; Spallanzani, Raúl G. ; Iraolagoitia, Ximena L. Raffo ; Rossi, Lucas E. ; Avila, Damián E. ; Torres, Nicolás I. ; Fuertes, Mercedes B. ; Zwirner, Norberto W.</creatorcontrib><description>IL‐27, a member of the IL‐12 family of cytokines, is produced by APCs, and displays pro‐ and anti‐inflammatory effects. How IL‐27 affects human NK cells still remains unknown. In this study, we observed that mature DCs secreted IL‐27 and that blockade of IL‐27R (CD130) reduced the amount of IFN‐γ produced by NK cells during their coculture, showing the importance of IL‐27 during DC–NK‐cell crosstalk. Accordingly, human rIL‐27 stimulated IFN‐γ secretion by NK cells in a STAT1‐dependent manner, induced upregulation of CD25 and CD69 on NK cells, and displayed a synergistic effect with IL‐18. Preincubation experiments demonstrated that IL‐27 primed NK cells for IL‐18‐induced IFN‐γ secretion, which was associated with an IL‐27‐driven upregulation of T‐bet expression. Also, IL‐27 triggered NKp46‐dependent NK‐cell‐mediated cytotoxicity against Raji, T‐47D, and HCT116 cells, and IL‐18 enhanced this cytotoxic response. Such NK‐cell‐mediated cytotoxicity involved upregulation of perforin, granule exocytosis, and TRAIL‐mediated cytotoxicity but not Fas‐FasL interaction. Moreover, IL‐27 also potentiated Ab‐dependent cell‐mediated cytotoxicity against mAb‐coated target cells. Taken together, IL‐27 stimulates NK‐cell effector functions, which might be relevant in different physiological and pathological situations.</description><identifier>ISSN: 0014-2980</identifier><identifier>EISSN: 1521-4141</identifier><identifier>DOI: 10.1002/eji.201444699</identifier><identifier>PMID: 25308526</identifier><identifier>CODEN: EJIMAF</identifier><language>eng</language><publisher>Germany: Wiley Subscription Services, Inc</publisher><subject>Antibodies, Monoclonal - pharmacology ; Antigens ; Antigens, CD - genetics ; Antigens, CD - immunology ; Antigens, Differentiation, T-Lymphocyte - genetics ; Antigens, Differentiation, T-Lymphocyte - immunology ; Cell Proliferation - drug effects ; Cell Survival - immunology ; Coculture Techniques ; Cytokine Receptor gp130 - genetics ; Cytokine Receptor gp130 - immunology ; Cytotoxicity ; Cytotoxicity, Immunologic ; Dendritic Cells - cytology ; Dendritic Cells - drug effects ; Dendritic Cells - immunology ; Gene Expression Regulation ; HCT116 Cells ; Humans ; IFN‐γ ; IL‐18 ; IL‐27 ; Immune system ; Interleukin-18 - immunology ; Interleukin-18 - pharmacology ; Interleukin-2 Receptor alpha Subunit - genetics ; Interleukin-2 Receptor alpha Subunit - immunology ; Interleukins - immunology ; Interleukins - pharmacology ; Killer Cells, Natural - cytology ; Killer Cells, Natural - drug effects ; Killer Cells, Natural - immunology ; Lectins, C-Type - genetics ; Lectins, C-Type - immunology ; NK cells ; Primary Cell Culture ; Recombinant Proteins - pharmacology ; Signal Transduction</subject><ispartof>European journal of immunology, 2015-01, Vol.45 (1), p.192-202</ispartof><rights>2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><rights>2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.</rights><rights>2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5067-b16338bb7bca7f9676a93f874190d3b6b809eaab2b7f0800c6751cfc61a3c6733</citedby><cites>FETCH-LOGICAL-c5067-b16338bb7bca7f9676a93f874190d3b6b809eaab2b7f0800c6751cfc61a3c6733</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Feji.201444699$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Feji.201444699$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,781,785,1418,1434,27929,27930,45579,45580,46414,46838</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25308526$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ziblat, Andrea</creatorcontrib><creatorcontrib>Domaica, Carolina I.</creatorcontrib><creatorcontrib>Spallanzani, Raúl G.</creatorcontrib><creatorcontrib>Iraolagoitia, Ximena L. Raffo</creatorcontrib><creatorcontrib>Rossi, Lucas E.</creatorcontrib><creatorcontrib>Avila, Damián E.</creatorcontrib><creatorcontrib>Torres, Nicolás I.</creatorcontrib><creatorcontrib>Fuertes, Mercedes B.</creatorcontrib><creatorcontrib>Zwirner, Norberto W.</creatorcontrib><title>IL‐27 stimulates human NK‐cell effector functions and primes NK cells for IL‐18 responsiveness</title><title>European journal of immunology</title><addtitle>Eur J Immunol</addtitle><description>IL‐27, a member of the IL‐12 family of cytokines, is produced by APCs, and displays pro‐ and anti‐inflammatory effects. How IL‐27 affects human NK cells still remains unknown. In this study, we observed that mature DCs secreted IL‐27 and that blockade of IL‐27R (CD130) reduced the amount of IFN‐γ produced by NK cells during their coculture, showing the importance of IL‐27 during DC–NK‐cell crosstalk. Accordingly, human rIL‐27 stimulated IFN‐γ secretion by NK cells in a STAT1‐dependent manner, induced upregulation of CD25 and CD69 on NK cells, and displayed a synergistic effect with IL‐18. Preincubation experiments demonstrated that IL‐27 primed NK cells for IL‐18‐induced IFN‐γ secretion, which was associated with an IL‐27‐driven upregulation of T‐bet expression. Also, IL‐27 triggered NKp46‐dependent NK‐cell‐mediated cytotoxicity against Raji, T‐47D, and HCT116 cells, and IL‐18 enhanced this cytotoxic response. Such NK‐cell‐mediated cytotoxicity involved upregulation of perforin, granule exocytosis, and TRAIL‐mediated cytotoxicity but not Fas‐FasL interaction. Moreover, IL‐27 also potentiated Ab‐dependent cell‐mediated cytotoxicity against mAb‐coated target cells. Taken together, IL‐27 stimulates NK‐cell effector functions, which might be relevant in different physiological and pathological situations.</description><subject>Antibodies, Monoclonal - pharmacology</subject><subject>Antigens</subject><subject>Antigens, CD - genetics</subject><subject>Antigens, CD - immunology</subject><subject>Antigens, Differentiation, T-Lymphocyte - genetics</subject><subject>Antigens, Differentiation, T-Lymphocyte - immunology</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Survival - immunology</subject><subject>Coculture Techniques</subject><subject>Cytokine Receptor gp130 - genetics</subject><subject>Cytokine Receptor gp130 - immunology</subject><subject>Cytotoxicity</subject><subject>Cytotoxicity, Immunologic</subject><subject>Dendritic Cells - cytology</subject><subject>Dendritic Cells - drug effects</subject><subject>Dendritic Cells - immunology</subject><subject>Gene Expression Regulation</subject><subject>HCT116 Cells</subject><subject>Humans</subject><subject>IFN‐γ</subject><subject>IL‐18</subject><subject>IL‐27</subject><subject>Immune system</subject><subject>Interleukin-18 - immunology</subject><subject>Interleukin-18 - pharmacology</subject><subject>Interleukin-2 Receptor alpha Subunit - genetics</subject><subject>Interleukin-2 Receptor alpha Subunit - immunology</subject><subject>Interleukins - immunology</subject><subject>Interleukins - pharmacology</subject><subject>Killer Cells, Natural - cytology</subject><subject>Killer Cells, Natural - drug effects</subject><subject>Killer Cells, Natural - immunology</subject><subject>Lectins, C-Type - genetics</subject><subject>Lectins, C-Type - immunology</subject><subject>NK cells</subject><subject>Primary Cell Culture</subject><subject>Recombinant Proteins - pharmacology</subject><subject>Signal Transduction</subject><issn>0014-2980</issn><issn>1521-4141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqN0btOIzEUBmAL7YpkgZIWWdqGZsLxfVwiBGwgggbqke3YYqK5hPEMKB2PsM-4T4KHsCm2QFvZsj_98vGP0DGBGQGgZ35VzigQzrnUeg9NiaAk44STb2gK6TyjOocJ-hHjCgC0FHofTahgkAsqp2g5X_x5-00Vjn1ZD5XpfcRPQ20afHebLpyvKuxD8K5vOxyGxvVl20RsmiVed2Wd9N0tHlXEIYmPNJLjzsd1cuWLb3yMh-h7MFX0R5_rAXq8uny4-JUt7q_nF-eLzAmQKrNEMpZbq6wzKmippNEs5IoTDUtmpc1Be2MstSpADuCkEsQFJ4lhac_YATrd5q679nnwsS_qMo6PM41vh1gQKbiUGpj-H0qZUpCPqT__oat26Jo0SFKcC6W1lEllW-W6NsbOh2L8H9NtCgLF2FSRmip2TSV_8pk62Novd_pvNQnQLXgtK7_5Oq24vJkzIhR7B8mZnnU</recordid><startdate>201501</startdate><enddate>201501</enddate><creator>Ziblat, Andrea</creator><creator>Domaica, Carolina I.</creator><creator>Spallanzani, Raúl G.</creator><creator>Iraolagoitia, Ximena L. Raffo</creator><creator>Rossi, Lucas E.</creator><creator>Avila, Damián E.</creator><creator>Torres, Nicolás I.</creator><creator>Fuertes, Mercedes B.</creator><creator>Zwirner, Norberto W.</creator><general>Wiley Subscription Services, Inc</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>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>201501</creationdate><title>IL‐27 stimulates human NK‐cell effector functions and primes NK cells for IL‐18 responsiveness</title><author>Ziblat, Andrea ; Domaica, Carolina I. ; Spallanzani, Raúl G. ; Iraolagoitia, Ximena L. 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Raffo</creatorcontrib><creatorcontrib>Rossi, Lucas E.</creatorcontrib><creatorcontrib>Avila, Damián E.</creatorcontrib><creatorcontrib>Torres, Nicolás I.</creatorcontrib><creatorcontrib>Fuertes, Mercedes B.</creatorcontrib><creatorcontrib>Zwirner, Norberto W.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ziblat, Andrea</au><au>Domaica, Carolina I.</au><au>Spallanzani, Raúl G.</au><au>Iraolagoitia, Ximena L. Raffo</au><au>Rossi, Lucas E.</au><au>Avila, Damián E.</au><au>Torres, Nicolás I.</au><au>Fuertes, Mercedes B.</au><au>Zwirner, Norberto W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>IL‐27 stimulates human NK‐cell effector functions and primes NK cells for IL‐18 responsiveness</atitle><jtitle>European journal of immunology</jtitle><addtitle>Eur J Immunol</addtitle><date>2015-01</date><risdate>2015</risdate><volume>45</volume><issue>1</issue><spage>192</spage><epage>202</epage><pages>192-202</pages><issn>0014-2980</issn><eissn>1521-4141</eissn><coden>EJIMAF</coden><abstract>IL‐27, a member of the IL‐12 family of cytokines, is produced by APCs, and displays pro‐ and anti‐inflammatory effects. How IL‐27 affects human NK cells still remains unknown. In this study, we observed that mature DCs secreted IL‐27 and that blockade of IL‐27R (CD130) reduced the amount of IFN‐γ produced by NK cells during their coculture, showing the importance of IL‐27 during DC–NK‐cell crosstalk. Accordingly, human rIL‐27 stimulated IFN‐γ secretion by NK cells in a STAT1‐dependent manner, induced upregulation of CD25 and CD69 on NK cells, and displayed a synergistic effect with IL‐18. Preincubation experiments demonstrated that IL‐27 primed NK cells for IL‐18‐induced IFN‐γ secretion, which was associated with an IL‐27‐driven upregulation of T‐bet expression. Also, IL‐27 triggered NKp46‐dependent NK‐cell‐mediated cytotoxicity against Raji, T‐47D, and HCT116 cells, and IL‐18 enhanced this cytotoxic response. Such NK‐cell‐mediated cytotoxicity involved upregulation of perforin, granule exocytosis, and TRAIL‐mediated cytotoxicity but not Fas‐FasL interaction. Moreover, IL‐27 also potentiated Ab‐dependent cell‐mediated cytotoxicity against mAb‐coated target cells. Taken together, IL‐27 stimulates NK‐cell effector functions, which might be relevant in different physiological and pathological situations.</abstract><cop>Germany</cop><pub>Wiley Subscription Services, Inc</pub><pmid>25308526</pmid><doi>10.1002/eji.201444699</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Antibodies, Monoclonal - pharmacology Antigens Antigens, CD - genetics Antigens, CD - immunology Antigens, Differentiation, T-Lymphocyte - genetics Antigens, Differentiation, T-Lymphocyte - immunology Cell Proliferation - drug effects Cell Survival - immunology Coculture Techniques Cytokine Receptor gp130 - genetics Cytokine Receptor gp130 - immunology Cytotoxicity Cytotoxicity, Immunologic Dendritic Cells - cytology Dendritic Cells - drug effects Dendritic Cells - immunology Gene Expression Regulation HCT116 Cells Humans IFN‐γ IL‐18 IL‐27 Immune system Interleukin-18 - immunology Interleukin-18 - pharmacology Interleukin-2 Receptor alpha Subunit - genetics Interleukin-2 Receptor alpha Subunit - immunology Interleukins - immunology Interleukins - pharmacology Killer Cells, Natural - cytology Killer Cells, Natural - drug effects Killer Cells, Natural - immunology Lectins, C-Type - genetics Lectins, C-Type - immunology NK cells Primary Cell Culture Recombinant Proteins - pharmacology Signal Transduction |
| title | IL‐27 stimulates human NK‐cell effector functions and primes NK cells for IL‐18 responsiveness |
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