{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:16:52Z","timestamp":1792023412783,"version":"4.4.0"},"reference-count":67,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T00:00:00Z","timestamp":1739145600000},"content-version":"vor","delay-in-days":707,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100015691","name":"HHS | NIH | NIAID | Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI146031"],"award-info":[{"award-number":["R01 AI146031"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015691","name":"HHS | NIH | NIAID | Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R21 AI149659"],"award-info":[{"award-number":["R21 AI149659"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015691","name":"HHS | NIH | NIAID | Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI143828"],"award-info":[{"award-number":["R01 AI143828"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["CA200922"],"award-info":[{"award-number":["CA200922"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>CMV infection alters NK cell phenotype and function toward a more memory-like immune state. These cells, termed adaptive NK cells, typically express CD57 and NKG2C but lack expression of the FcR\u03b3-chain (gene: FCER1G, FcR\u03b3), PLZF, and SYK. Functionally, adaptive NK cells display enhanced Ab-dependent cellular cytotoxicity (ADCC) and cytokine production. However, the mechanism behind this enhanced function is unknown. To understand what drives enhanced ADCC and cytokine production in adaptive NK cells, we optimized a CRISPR\/Cas9 system to ablate genes from primary human NK cells. We ablated genes that encode molecules in the ADCC pathway, such as FcR\u03b3, CD3\u03b6, SYK, SHP-1, ZAP70, and the transcription factor PLZF, and tested subsequent ADCC and cytokine production. We found that ablating the FcR\u03b3-chain caused a modest increase in TNF-\u03b1 production. Ablation of PLZF did not enhance ADCC or cytokine production. Importantly, SYK kinase ablation significantly enhanced cytotoxicity, cytokine production, and target cell conjugation, whereas ZAP70 kinase ablation diminished function. Ablating the phosphatase SHP-1 enhanced cytotoxicity but reduced cytokine production. These results indicate that the enhanced cytotoxicity and cytokine production of CMV-induced adaptive NK cells is more likely due to the loss of SYK than the lack of FcR\u03b3 or PLZF. We found the lack of SYK expression could improve target cell conjugation through enhanced CD2 expression or limit SHP-1\u2013mediated inhibition of CD16A signaling, leading to enhanced cytotoxicity and cytokine production.<\/jats:p>","DOI":"10.4049\/jimmunol.2200488","type":"journal-article","created":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T22:18:15Z","timestamp":1678227495000},"page":"1108-1122","source":"Crossref","is-referenced-by-count":16,"title":["Ablation of SYK Kinase from Expanded Primary Human NK Cells via CRISPR\/Cas9 Enhances Cytotoxicity and Cytokine Production"],"prefix":"10.1093","volume":"210","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2702-6943","authenticated-orcid":false,"given":"James D","family":"Dahlvang","sequence":"first","affiliation":[{"name":"Division of Infectious Disease and International Medicine, Department of Medicine, University of Minnesota , Minneapolis, MN"},{"name":"Center for Immunology, University of Minnesota , Minneapolis, MN"},{"name":"Masonic Cancer Center, University of Minnesota , Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2553-7536","authenticated-orcid":false,"given":"Jenna K","family":"Dick","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease and International Medicine, Department of Medicine, University of Minnesota , Minneapolis, MN"},{"name":"Center for Immunology, University of Minnesota , Minneapolis, MN"},{"name":"Masonic Cancer Center, University of Minnesota , Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6432-4966","authenticated-orcid":false,"given":"Jules A","family":"Sangala","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease and International Medicine, Department of Medicine, University of Minnesota , Minneapolis, MN"},{"name":"Center for Immunology, University of Minnesota , Minneapolis, MN"},{"name":"Masonic Cancer Center, University of Minnesota , Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0239-5440","authenticated-orcid":false,"given":"Philippa R","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Center for Immunology, University of Minnesota , Minneapolis, MN"},{"name":"Masonic Cancer Center, University of Minnesota , Minneapolis, MN"},{"name":"Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota , Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7690-3570","authenticated-orcid":false,"given":"Emily J","family":"Pomeroy","sequence":"additional","affiliation":[{"name":"Masonic Cancer Center, University of Minnesota , Minneapolis, MN"},{"name":"Department of Pediatrics, Masonic Cancer Center, University of Minnesota , Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin M","family":"Snyder","sequence":"additional","affiliation":[{"name":"Center for Immunology, University of Minnesota , Minneapolis, MN"},{"name":"Department of Veterinary and Biological Sciences, University of Minnesota , St. Paul, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6871-0872","authenticated-orcid":false,"given":"Juliette M","family":"Moushon","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease and International Medicine, Department of Medicine, University of Minnesota , Minneapolis, MN"},{"name":"Center for Immunology, University of Minnesota , Minneapolis, MN"},{"name":"Masonic Cancer Center, University of Minnesota , Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2162-4325","authenticated-orcid":false,"given":"Claire E","family":"Thefaine","sequence":"additional","affiliation":[{"name":"Center for Immunology, University of Minnesota , Minneapolis, MN"},{"name":"Masonic Cancer Center, University of Minnesota , Minneapolis, MN"},{"name":"Department of Laboratory Medicine and Pathology, University of Minnesota , Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9142-7066","authenticated-orcid":false,"given":"Jianming","family":"Wu","sequence":"additional","affiliation":[{"name":"Masonic Cancer Center, University of Minnesota , Minneapolis, MN"},{"name":"Department of Veterinary and Biological Sciences, University of Minnesota , St. Paul, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3768-7622","authenticated-orcid":false,"given":"Sara E","family":"Hamilton","sequence":"additional","affiliation":[{"name":"Center for Immunology, University of Minnesota , Minneapolis, MN"},{"name":"Masonic Cancer Center, University of Minnesota , Minneapolis, MN"},{"name":"Department of Laboratory Medicine and Pathology, University of Minnesota , Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5945-0634","authenticated-orcid":false,"given":"Martin","family":"Felices","sequence":"additional","affiliation":[{"name":"Center for Immunology, University of Minnesota , Minneapolis, MN"},{"name":"Masonic Cancer Center, University of Minnesota , Minneapolis, MN"},{"name":"Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota , Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0339-4944","authenticated-orcid":false,"given":"Jeffrey S","family":"Miller","sequence":"additional","affiliation":[{"name":"Center for Immunology, University of Minnesota , Minneapolis, MN"},{"name":"Masonic Cancer Center, University of Minnesota , Minneapolis, MN"},{"name":"Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota , Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1933-3887","authenticated-orcid":false,"given":"Bruce","family":"Walcheck","sequence":"additional","affiliation":[{"name":"Center for Immunology, University of Minnesota , Minneapolis, MN"},{"name":"Masonic Cancer Center, University of Minnesota , Minneapolis, MN"},{"name":"Department of Veterinary and Biological Sciences, University of Minnesota , St. Paul, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beau R","family":"Webber","sequence":"additional","affiliation":[{"name":"Masonic Cancer Center, University of Minnesota , Minneapolis, MN"},{"name":"Department of Pediatrics, Masonic Cancer Center, University of Minnesota , Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Branden S","family":"Moriarity","sequence":"additional","affiliation":[{"name":"Masonic Cancer Center, University of Minnesota , Minneapolis, MN"},{"name":"Department of Pediatrics, Masonic Cancer Center, University of Minnesota , Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0483-307X","authenticated-orcid":false,"given":"Geoffrey T","family":"Hart","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease and International Medicine, Department of Medicine, University of Minnesota , Minneapolis, MN"},{"name":"Center for Immunology, University of Minnesota , Minneapolis, MN"},{"name":"Masonic Cancer Center, University of Minnesota , Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,3,6]]},"reference":[{"key":"2025021101014278000_r1","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.3389\/fimmu.2018.01869","article-title":"Natural killer cells: development, maturation, and clinical utilization","volume":"9","author":"Abel","year":"2018","journal-title":"Front. Immunol."},{"key":"2025021101014278000_r2","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/ni1581","article-title":"Up on the tightrope: natural killer cell activation and inhibition","volume":"9","author":"Lanier","year":"2008","journal-title":"Nat. Immunol."},{"key":"2025021101014278000_r3","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1146\/annurev-immunol-101819-074948","article-title":"Natural killer cells: from innate to adaptive features","volume":"39","author":"Mujal","year":"2021","journal-title":"Annu. Rev. Immunol."},{"key":"2025021101014278000_r4","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1177\/17534259211001512","article-title":"Human NK cells: from development to effector functions","volume":"27","author":"Perera Molligoda Arachchige","year":"2021","journal-title":"Innate Immun."},{"key":"2025021101014278000_r5","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1186\/s12936-019-2953-1","article-title":"Contributions of natural killer cells to the immune response against Plasmodium","volume":"18","author":"Burrack","year":"2019","journal-title":"Malar. J."},{"key":"2025021101014278000_r6","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.4049\/jimmunol.146.5.1571","article-title":"Analysis of Fc gamma RIII (CD16) membrane expression and association with CD3 zeta and Fc epsilon RI-gamma by site-directed mutation","volume":"146","author":"Lanier","year":"1991","journal-title":"J. Immunol."},{"key":"2025021101014278000_r7","doi-asserted-by":"crossref","first-page":"a002485","DOI":"10.1101\/cshperspect.a002485","article-title":"ITAM-mediated signaling by the T-cell antigen receptor","volume":"2","author":"Love","year":"2010","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"2025021101014278000_r8","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1128\/MCB.15.1.272","article-title":"Interaction of p72syk with the gamma and beta subunits of the high-affinity receptor for immunoglobulin E, Fc epsilon RI","volume":"15","author":"Shiue","year":"1995","journal-title":"Mol. Cell. Biol."},{"key":"2025021101014278000_r9","doi-asserted-by":"crossref","DOI":"10.1002\/0471142735.im1109bs90","article-title":"Signal transduction during activation and inhibition of natural killer cells","author":"Watzl","year":"2010","journal-title":"Curr. Protoc. Immunol."},{"key":"2025021101014278000_r10","doi-asserted-by":"crossref","first-page":"e09183","DOI":"10.7554\/eLife.09183","article-title":"LynA regulates an inflammation-sensitive signaling checkpoint in macrophages","volume":"4","author":"Freedman","year":"2015","journal-title":"eLife"},{"key":"2025021101014278000_r11","doi-asserted-by":"crossref","first-page":"3931","DOI":"10.1038\/s41467-019-11947-7","article-title":"Heterogeneity of human bone marrow and blood natural killer cells defined by single-cell transcriptome","volume":"10","author":"Yang","year":"2019","journal-title":"Nat. Commun."},{"key":"2025021101014278000_r12","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/nature07665","article-title":"Adaptive immune features of natural killer cells. [Published erratum appears in 2009 Nature 457: 1168.]","volume":"457","author":"Sun","year":"2009","journal-title":"Nature"},{"key":"2025021101014278000_r13","doi-asserted-by":"crossref","first-page":"14725","DOI":"10.1073\/pnas.1110900108","article-title":"Expansion of a unique CD57+NKG2Chi natural killer cell subset during acute human cytomegalovirus infection","volume":"108","author":"Lopez-Verg\u00e8s","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025021101014278000_r14","doi-asserted-by":"crossref","first-page":"3664","DOI":"10.1182\/blood-2004-05-2058","article-title":"Imprint of human cytomegalovirus infection on the NK cell receptor repertoire","volume":"104","author":"Gum\u00e1","year":"2004","journal-title":"Blood"},{"key":"2025021101014278000_r15","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1002\/eji.200939898","article-title":"Influence of human cytomegalovirus infection on the NK cell receptor repertoire in children","volume":"40","author":"Monsiv\u00e1is-Urenda","year":"2010","journal-title":"Eur. J. Immunol."},{"key":"2025021101014278000_r16","doi-asserted-by":"crossref","first-page":"3624","DOI":"10.1182\/blood-2005-09-3682","article-title":"Expansion of CD94\/NKG2C+ NK cells in response to human cytomegalovirus-infected fibroblasts","volume":"107","author":"Gum\u00e1","year":"2006","journal-title":"Blood"},{"key":"2025021101014278000_r17","doi-asserted-by":"crossref","first-page":"2665","DOI":"10.1182\/blood-2011-10-386995","article-title":"Cytomegalovirus reactivation after allogeneic transplantation promotes a lasting increase in educated NKG2C+ natural killer cells with potent function","volume":"119","author":"Foley","year":"2012","journal-title":"Blood"},{"key":"2025021101014278000_r18","doi-asserted-by":"crossref","first-page":"e125553","DOI":"10.1172\/jci.insight.125553","article-title":"Adaptive NK cell reconstitution is associated with better clinical outcomes","volume":"4","author":"Cichocki","year":"2019","journal-title":"JCI Insight"},{"key":"2025021101014278000_r19","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1093\/intimm\/dxs080","article-title":"Identification of human NK cells that are deficient for signaling adaptor FcR\u03b3 and specialized for antibody-dependent immune functions","volume":"24","author":"Hwang","year":"2012","journal-title":"Int. Immunol."},{"key":"2025021101014278000_r20","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.4049\/jimmunol.1203034","article-title":"Cutting edge: antibody-dependent memory-like NK cells distinguished by FcR\u03b3 deficiency","volume":"190","author":"Zhang","year":"2013","journal-title":"J. Immunol."},{"key":"2025021101014278000_r21","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.immuni.2015.02.013","article-title":"Epigenetic modification and antibody-dependent expansion of memory-like NK cells in human cytomegalovirus-infected individuals","volume":"42","author":"Lee","year":"2015","journal-title":"Immunity"},{"key":"2025021101014278000_r22","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.immuni.2015.02.008","article-title":"Cytomegalovirus infection drives adaptive epigenetic diversification of NK cells with altered signaling and effector function","volume":"42","author":"Schlums","year":"2015","journal-title":"Immunity"},{"key":"2025021101014278000_r23","doi-asserted-by":"crossref","first-page":"E5980","DOI":"10.1073\/pnas.1720564115","article-title":"Distinct human circulating NKp30+Fc\u03b5RI\u03b3+CD8+ T cell population exhibiting high natural killer-like antitumor potential","volume":"115","author":"Correia","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025021101014278000_r24","doi-asserted-by":"crossref","first-page":"4688","DOI":"10.4049\/jimmunol.1402448","article-title":"An NK cell population lacking FcR\u03b3 is expanded in chronically infected HIV patients","volume":"194","author":"Zhou","year":"2015","journal-title":"J. Immunol."},{"key":"2025021101014278000_r25","doi-asserted-by":"crossref","first-page":"e36806","DOI":"10.7554\/eLife.36806","article-title":"NK cells inhibit Plasmodium falciparum growth in red blood cells via antibody-dependent cellular cytotoxicity","volume":"7","author":"Arora","year":"2018","journal-title":"eLife"},{"key":"2025021101014278000_r26","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1084\/jem.20181681","article-title":"Adaptive NK cells in people exposed to Plasmodium falciparum correlate with protection from malaria","volume":"216","author":"Hart","year":"2019","journal-title":"J. Exp. Med."},{"key":"2025021101014278000_r27","doi-asserted-by":"crossref","first-page":"e20220022","DOI":"10.1084\/jem.20220022","article-title":"The CD3\u03b6 adaptor structure determines functional differences between human and mouse CD16 Fc receptor signaling","volume":"219","author":"Aguilar","year":"2022","journal-title":"J. Exp. Med."},{"key":"2025021101014278000_r28","volume-title":"R: A Language and Environment for Statistical Computing","author":"R Core Team","year":"2021"},{"key":"2025021101014278000_r29","article-title":"Introduction to R 2021: 19.11 Volcano plots","author":"Bonnin","year":"2020"},{"key":"2025021101014278000_r30","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.ymthe.2019.10.009","article-title":"A genetically engineered primary human natural killer cell platform for cancer immunotherapy","volume":"28","author":"Pomeroy","year":"2020","journal-title":"Mol. Ther."},{"key":"2025021101014278000_r31","doi-asserted-by":"crossref","first-page":"6392","DOI":"10.4049\/jimmunol.180.9.6392","article-title":"Blocking NK cell inhibitory self-recognition promotes antibody-dependent cellular cytotoxicity in a model of anti-lymphoma therapy","volume":"180","author":"Binyamin","year":"2008","journal-title":"J. Immunol."},{"key":"2025021101014278000_r32","doi-asserted-by":"crossref","first-page":"2873","DOI":"10.3389\/fimmu.2018.02873","article-title":"Expression of a recombinant high affinity IgG Fc receptor by engineered NK cells as a docking platform for therapeutic mAbs to target cancer cells","volume":"9","author":"Snyder","year":"2018","journal-title":"Front. Immunol."},{"key":"2025021101014278000_r33","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/978-1-60761-362-6_7","article-title":"Natural killer cell conjugate assay using two-color flow cytometry","volume":"612","author":"Burshtyn","year":"2010","journal-title":"Methods Mol. Biol."},{"key":"2025021101014278000_r34","doi-asserted-by":"crossref","first-page":"101709","DOI":"10.1016\/j.isci.2020.101709","article-title":"FcR\u03b3 gene editing reprograms conventional NK cells to display key features of adaptive human NK cells","volume":"23","author":"Liu","year":"2020","journal-title":"iScience"},{"key":"2025021101014278000_r35","doi-asserted-by":"crossref","first-page":"e20201529","DOI":"10.1084\/jem.20201529","article-title":"A robust platform for expansion and genome editing of primary human natural killer cells","volume":"218","author":"Huang","year":"2021","journal-title":"J. Exp. Med."},{"issue":"136","key":"2025021101014278000_r36","first-page":"58237","article-title":"Generation of knock-out primary and expanded human NK cells using Cas9 ribonucleoproteins","author":"Naeimi Kararoudi","year":"2018","journal-title":"J. Vis. Exp."},{"key":"2025021101014278000_r37","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1158\/2326-6066.CIR-21-0178","article-title":"Simultaneous engagement of tumor and stroma targeting antibodies by engineered NK-92 cells expressing CD64 controls prostate cancer growth","volume":"9","author":"Hintz","year":"2021","journal-title":"Cancer Immunol. Res."},{"key":"2025021101014278000_r38","doi-asserted-by":"crossref","first-page":"3599","DOI":"10.1182\/blood-2012-04-425397","article-title":"NK cell CD16 surface expression and function is regulated by a disintegrin and metalloprotease-17 (ADAM17)","volume":"121","author":"Romee","year":"2013","journal-title":"Blood"},{"key":"2025021101014278000_r39","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1016\/j.bbamcr.2012.11.027","article-title":"ADAM17 cleaves CD16b (Fc\u03b3RIIIb) in human neutrophils","volume":"1833","author":"Wang","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"2025021101014278000_r40","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1038\/342803a0","article-title":"Co-association of CD3\u03b6 with a receptor (CD16) for IgG Fc on human natural killer cells","volume":"342","author":"Lanier","year":"1989","journal-title":"Nature"},{"key":"2025021101014278000_r41","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1126\/science.2531918","article-title":"Mechanisms for regulating expression of membrane isoforms of Fc\u03b3RIII (CD16)","volume":"246","author":"Hibbs","year":"1989","journal-title":"Science"},{"key":"2025021101014278000_r42","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1038\/342805a0","article-title":"A single amino acid in the glycosyl phosphatidylinositol attachment domain determines the membrane topology of Fc\u03b3RIII. [Published erratum appears in 1990 Nature 343: 390.]","volume":"342","author":"Kurosaki","year":"1989","journal-title":"Nature"},{"key":"2025021101014278000_r43","doi-asserted-by":"crossref","first-page":"384","DOI":"10.3389\/fimmu.2016.00384","article-title":"Sustained immune complex-mediated reduction in CD16 expression after vaccination regulates NK cell function","volume":"7","author":"Goodier","year":"2016","journal-title":"Front. Immunol."},{"key":"2025021101014278000_r44","doi-asserted-by":"crossref","first-page":"368","DOI":"10.3389\/fimmu.2015.00368","article-title":"NK cell-mediated antibody-dependent cellular cytotoxicity in cancer immunotherapy","volume":"6","author":"Wang","year":"2015","journal-title":"Front. Immunol."},{"key":"2025021101014278000_r45","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1016\/j.celrep.2016.04.005","article-title":"Critical role of CD2 co-stimulation in adaptive natural killer cell responses revealed in NKG2C-deficient humans","volume":"15","author":"Liu","year":"2016","journal-title":"Cell Rep."},{"key":"2025021101014278000_r46","doi-asserted-by":"crossref","first-page":"14151","DOI":"10.1073\/pnas.1835830100","article-title":"The mature activating natural killer cell immunologic synapse is formed in distinct stages","volume":"100","author":"Orange","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025021101014278000_r47","doi-asserted-by":"crossref","first-page":"54","DOI":"10.3390\/antib9040054","article-title":"Natural killer (NK) cell expression of CD2 as a predictor of serial antibody-dependent cell-mediated cytotoxicity (ADCC)","volume":"9","author":"Tang","year":"2020","journal-title":"Antibodies (Basel)"},{"key":"2025021101014278000_r48","doi-asserted-by":"crossref","first-page":"2539","DOI":"10.1002\/(SICI)1521-4141(199908)29:08<2539::AID-IMMU2539>3.0.CO;2-M","article-title":"Dephosphorylation of ZAP-70 and inhibition of T cell activation by activated SHP1","volume":"29","author":"Brockdorff","year":"1999","journal-title":"Eur. J. Immunol."},{"key":"2025021101014278000_r49","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1126\/science.272.5265.1173","article-title":"Direct regulation of ZAP-70 by SHP-1 in T cell antigen receptor signaling","volume":"272","author":"Plas","year":"1996","journal-title":"Science"},{"key":"2025021101014278000_r50","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1038\/nm1665","article-title":"CD16 promotes Escherichia coli sepsis through an FcR\u03b3 inhibitory pathway that prevents phagocytosis and facilitates inflammation","volume":"13","author":"Pinheiro da Silva","year":"2007","journal-title":"Nat. Med."},{"key":"2025021101014278000_r51","doi-asserted-by":"crossref","first-page":"2669","DOI":"10.4049\/jimmunol.180.4.2669","article-title":"Inhibitory ITAM signaling by Fc\u03b1RI-FcR\u03b3 chain controls multiple activating responses and prevents renal inflammation","volume":"180","author":"Kanamaru","year":"2008","journal-title":"J. Immunol."},{"key":"2025021101014278000_r52","doi-asserted-by":"crossref","first-page":"3084","DOI":"10.1182\/blood-2011-08-376046","article-title":"IgG1 and IVIg induce inhibitory ITAM signaling through Fc\u03b3RIII controlling inflammatory responses","volume":"119","author":"Aloulou","year":"2012","journal-title":"Blood"},{"key":"2025021101014278000_r53","doi-asserted-by":"crossref","first-page":"re2","DOI":"10.1126\/stke.3772007re2","article-title":"The expanding role for ITAM-based signaling pathways in immune cells","volume":"2007","author":"Abram","year":"2007","journal-title":"Sci. STKE"},{"key":"2025021101014278000_r54","doi-asserted-by":"crossref","first-page":"pe20","DOI":"10.1126\/scisignal.2001917","article-title":"How ITAMs inhibit signaling","volume":"4","author":"Ivashkiv","year":"2011","journal-title":"Sci. Signal."},{"key":"2025021101014278000_r55","doi-asserted-by":"crossref","first-page":"3945","DOI":"10.1172\/JCI74572","article-title":"Shifting Fc\u03b3RIIA-ITAM from activation to inhibitory configuration ameliorates arthritis","volume":"124","author":"Ben Mkaddem","year":"2014","journal-title":"J. Clin. Invest."},{"key":"2025021101014278000_r56","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1038\/s41467-017-00294-0","article-title":"Lyn and Fyn function as molecular switches that control immunoreceptors to direct homeostasis or inflammation","volume":"8","author":"Mkaddem","year":"2017","journal-title":"Nat. Commun."},{"key":"2025021101014278000_r57","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13045-020-01014-w","article-title":"NK cell-based cancer immunotherapy: from basic biology to clinical development","volume":"14","author":"Liu","year":"2021","journal-title":"J. Hematol. Oncol."},{"key":"2025021101014278000_r58","doi-asserted-by":"crossref","first-page":"3051","DOI":"10.1182\/blood-2004-07-2974","article-title":"Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer","volume":"105","author":"Miller","year":"2005","journal-title":"Blood"},{"key":"2025021101014278000_r59","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.3389\/fimmu.2019.01025","article-title":"Knowns and unknowns of assaying antibody-dependent cell-mediated cytotoxicity against HIV-1","volume":"10","author":"Lewis","year":"2019","journal-title":"Front. Immunol."},{"key":"2025021101014278000_r60","doi-asserted-by":"crossref","first-page":"3126","DOI":"10.4049\/jimmunol.1900985","article-title":"Functional attributes of antibodies, effector cells, and target cells affecting NK cell-mediated antibody-dependent cellular cytotoxicity","volume":"203","author":"Temming","year":"2019","journal-title":"J. Immunol."},{"key":"2025021101014278000_r61","doi-asserted-by":"crossref","first-page":"e146973","DOI":"10.1172\/jci.insight.146973","article-title":"Single-cell profiling identifies impaired adaptive NK cells expanded after HCMV reactivation in haploidentical HSCT","volume":"6","author":"Zaghi","year":"2021","journal-title":"JCI Insight"},{"key":"2025021101014278000_r62","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.1182\/blood-2009-08-238469","article-title":"Regulation of human NK-cell cytokine and chemokine production by target cell recognition","volume":"115","author":"Fauriat","year":"2010","journal-title":"Blood"},{"key":"2025021101014278000_r63","doi-asserted-by":"crossref","first-page":"e0121788","DOI":"10.1371\/journal.pone.0121788","article-title":"Identification of an ADAM17 cleavage region in human CD16 (Fc\u03b3RIII) and the engineering of a non-cleavable version of the receptor in NK cells","volume":"10","author":"Jing","year":"2015","journal-title":"PLoS One"},{"key":"2025021101014278000_r64","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1002\/JLB.2MR1218-501R","article-title":"Role of ADAM17 as a regulatory checkpoint of CD16A in NK cells and as a potential target for cancer immunotherapy","volume":"105","author":"Wu","year":"2019","journal-title":"J. Leukoc. Biol."},{"key":"2025021101014278000_r65","doi-asserted-by":"crossref","first-page":"e44244","DOI":"10.1371\/journal.pone.0044244","article-title":"SHP-1 phosphatase is a critical regulator in preventing natural killer cell self-killing","volume":"7","author":"Mahmood","year":"2012","journal-title":"PLoS One"},{"key":"2025021101014278000_r66","doi-asserted-by":"crossref","first-page":"eaal2880","DOI":"10.1126\/scisignal.aal2880","article-title":"The tyrosine phosphatase SHP-1 promotes T cell adhesion by activating the adaptor protein CrkII in the immunological synapse","volume":"10","author":"Azoulay-Alfaguter","year":"2017","journal-title":"Sci. Signal."},{"key":"2025021101014278000_r67","doi-asserted-by":"crossref","first-page":"eaaw9252","DOI":"10.1126\/scisignal.aaw9252","article-title":"Genetic diversity affects the nanoscale membrane organization and signaling of natural killer cell receptors","volume":"12","author":"Kennedy","year":"2019","journal-title":"Sci. Signal."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/210\/8\/1108\/61469808\/ji2200488.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/210\/8\/1108\/61469808\/ji2200488.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T01:02:55Z","timestamp":1739235775000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/210\/8\/1108\/7932645"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,6]]},"references-count":67,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2023,4,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.2200488","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,4]]},"published":{"date-parts":[[2023,3,6]]}}}