{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T23:42:39Z","timestamp":1774136559037,"version":"3.50.1"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2019,11,15]],"date-time":"2019-11-15T00:00:00Z","timestamp":1573776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"},{"start":{"date-parts":[[2019,11,15]],"date-time":"2019-11-15T00:00:00Z","timestamp":1573776000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2019,11,15]],"date-time":"2019-11-15T00:00:00Z","timestamp":1573776000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"name":"National Key Research & Developmental Program of China","award":["2018YFC1003900"],"award-info":[{"award-number":["2018YFC1003900"]}]},{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81725007"],"award-info":[{"award-number":["81725007"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31830027"],"award-info":[{"award-number":["31830027"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31821003"],"award-info":[{"award-number":["31821003"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81901671"],"award-info":[{"award-number":["81901671"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Beijing Natural Science Foundation","doi-asserted-by":"publisher","award":["5172018"],"award-info":[{"award-number":["5172018"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012152","name":"Postdoctoral Innovation Talent Support Program of China","doi-asserted-by":"crossref","award":["BX201700134"],"award-info":[{"award-number":["BX201700134"]}],"id":[{"id":"10.13039\/501100012152","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2017M620051"],"award-info":[{"award-number":["2017M620051"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81725007"],"award-info":[{"award-number":["81725007"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31830027"],"award-info":[{"award-number":["31830027"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31821003"],"award-info":[{"award-number":["31821003"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81901671"],"award-info":[{"award-number":["81901671"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["5172018"],"award-info":[{"award-number":["5172018"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2017M620051"],"award-info":[{"award-number":["2017M620051"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>NK cells recognize \u201cunwanted\u201d cells using a variety of germline-encoded activating receptors, such as the seven members of signaling lymphocyte activating molecule (SLAM)-family receptors (SFRs), natural killer cell group 2D (NKG2D), and DNAX accessory molecule-1(DNAM-1). Whether these receptors redundantly or synergistically regulate NK cell development and effector function remains poorly understood. By generating mice lacking SFRs, NKG2D, and DNAM-1, separately or in combination, we found that SLAMF6, one of the SFR members, was associated with NK cell differentiation, but its absence had no severe effect on NK cell differentiation and function, likely due to SFR redundancy. Moreover, we revealed that SFRs might work with other NK cell activating receptors in regulating NK cell development and function. We found that SFR deficiency caused an increase in immature NK cell subsets (CD27+CD11b\u2212), and this effect was further augmented by the additional deficiency of NKG2D but not DNAM-1. However, SFR-deficient NK cells exhibited elevated responsiveness against \u201cmissing-self\u201d hematopoietic targets, whereas the deletion of either NKG2D or DNAM-1 could partially abrogate the elevated effect of SFR deficiency on NK cell activation. Therefore, our results reveal the complexity of activating receptors in regulating NK cell differentiation and activation, extending our insights into the gene redundancy and compensatory effect of NK cell activating receptors.<\/jats:p>","DOI":"10.1002\/jlb.1ma1019-186r","type":"journal-article","created":{"date-parts":[[2019,11,15]],"date-time":"2019-11-15T11:46:43Z","timestamp":1573818403000},"page":"561-572","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Concomitant deletion of SLAM-family receptors, NKG2D and DNAM-1 reveals gene redundancy of NK cell activating receptors in NK cell development and education"],"prefix":"10.1093","volume":"107","author":[{"given":"Shasha","family":"Chen","sequence":"first","affiliation":[{"name":"School of Medicine and Institute for Immunology, Tsinghua University , Beijing, China"},{"name":"Tsinghua University-Peking University Joint Center for Life Sciences, Tsinghua University , Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2155-231X","authenticated-orcid":false,"given":"Zhongjun","family":"Dong","sequence":"additional","affiliation":[{"name":"School of Medicine and Institute for Immunology, Tsinghua University , Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,11,15]]},"reference":[{"issue":"5","key":"2023012312514680200_jlb10509-bib-0001","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/ni1582","article-title":"Functions of natural killer cells","volume":"9","author":"Vivier","year":"2008","journal-title":"Nat Immunol"},{"key":"2023012312514680200_jlb10509-bib-0002","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1146\/annurev.immunol.23.021704.115526","article-title":"NK cell recognition","volume":"23","author":"Lanier","year":"2005","journal-title":"Annu Rev Immunol"},{"key":"2023012312514680200_jlb10509-bib-0003","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1146\/annurev-immunol-020711-075005","article-title":"Controlling natural killer cell responses: integration of signals for activation and inhibition","volume":"31","author":"Long","year":"2013","journal-title":"Ann Rev Immunol"},{"issue":"22","key":"2023012312514680200_jlb10509-bib-0004","doi-asserted-by":"crossref","first-page":"4324","DOI":"10.1182\/blood-2012-06-438028","article-title":"A phase 1 trial of the anti-KIR antibody IPH2101 in patients with relapsed\/refractory multiple myeloma","volume":"120","author":"Benson","year":"2012","journal-title":"Blood"},{"issue":"5","key":"2023012312514680200_jlb10509-bib-0005","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1182\/blood-2013-08-519199","article-title":"Anti-KIR antibody enhancement of anti-lymphoma activity of natural killer cells as monotherapy and in combination with anti-CD20 antibodies","volume":"123","author":"Kohrt","year":"2014","journal-title":"Blood"},{"issue":"13","key":"2023012312514680200_jlb10509-bib-0006","doi-asserted-by":"crossref","first-page":"2667","DOI":"10.1182\/blood-2009-02-206532","article-title":"Preclinical characterization of 1\u20137F9, a novel human anti-KIR receptor therapeutic antibody that augments natural killer-mediated killing of tumor cells","volume":"114","author":"Romagne","year":"2009","journal-title":"Blood"},{"issue":"5","key":"2023012312514680200_jlb10509-bib-0007","doi-asserted-by":"crossref","first-page":"626","DOI":"10.3324\/haematol.2015.135301","article-title":"Effects of anti-NKG2A antibody administration on leukemia and normal hematopoietic cells","volume":"101","author":"Ruggeri","year":"2016","journal-title":"Haematologica"},{"issue":"22","key":"2023012312514680200_jlb10509-bib-0008","doi-asserted-by":"crossref","first-page":"4317","DOI":"10.1182\/blood-2012-06-437558","article-title":"A phase 1 trial of the anti-inhibitory KIR mAb IPH2101 for AML in complete remission","volume":"120","author":"Vey","year":"2012","journal-title":"Blood"},{"issue":"6013","key":"2023012312514680200_jlb10509-bib-0009","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1126\/science.1198687","article-title":"Innate or adaptive immunity? The example of natural killer cells","volume":"331","author":"Vivier","year":"2011","journal-title":"Science"},{"issue":"10","key":"2023012312514680200_jlb10509-bib-0010","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1038\/nri1199","article-title":"Roles of the NKG2D immunoreceptor and its ligands","volume":"3","author":"Raulet","year":"2003","journal-title":"Nat Rev Immunol"},{"key":"2023012312514680200_jlb10509-bib-0011","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1146\/annurev.immunol.19.1.197","article-title":"Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis","volume":"19","author":"Moretta","year":"2001","journal-title":"Annu Rev Immunol"},{"issue":"2","key":"2023012312514680200_jlb10509-bib-0012","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.immuni.2009.06.017","article-title":"Altered NK cell development and enhanced NK cell-mediated resistance to mouse cytomegalovirus in NKG2D-deficient mice","volume":"31","author":"Zafirova","year":"2009","journal-title":"Immunity"},{"issue":"13","key":"2023012312514680200_jlb10509-bib-0013","doi-asserted-by":"crossref","first-page":"2959","DOI":"10.1084\/jem.20081611","article-title":"Accelerated tumor growth in mice deficient in DNAM-1 receptor","volume":"205","author":"Iguchi-Manaka","year":"2008","journal-title":"J Exp Med"},{"issue":"4","key":"2023012312514680200_jlb10509-bib-0014","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.immuni.2008.02.016","article-title":"NKG2D-deficient mice are defective in tumor surveillance in models of spontaneous malignancy","volume":"28","author":"Guerra","year":"2008","journal-title":"Immunity"},{"issue":"25","key":"2023012312514680200_jlb10509-bib-0015","doi-asserted-by":"crossref","first-page":"5025","DOI":"10.1182\/blood-2012-12-471607","article-title":"Characterization of a novel NKG2D and NKp46 double-mutant mouse reveals subtle variations in the NK cell repertoire","volume":"121","author":"Sheppard","year":"2013","journal-title":"Blood"},{"issue":"9","key":"2023012312514680200_jlb10509-bib-0016","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1038\/ni.1763","article-title":"Essential function for SAP family adaptors in the surveillance of hematopoietic cells by natural killer cells","volume":"10","author":"Dong","year":"2009","journal-title":"Nat Immunol"},{"key":"2023012312514680200_jlb10509-bib-0017","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1146\/annurev-immunol-030409-101302","article-title":"SLAM family receptors and SAP adaptors in immunity","volume":"29","author":"Cannons","year":"2011","journal-title":"Annu Rev Immunol"},{"issue":"8","key":"2023012312514680200_jlb10509-bib-0018","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.it.2010.05.008","article-title":"How do SAP family deficiencies compromise immunity","volume":"31","author":"Dong","year":"2010","journal-title":"Trends Immunol"},{"issue":"6","key":"2023012312514680200_jlb10509-bib-0019","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1016\/j.immuni.2012.03.023","article-title":"The adaptor SAP controls NK cell activation by regulating the enzymes Vav-1 and SHIP-1 and by enhancing conjugates with target cells","volume":"36","author":"Dong","year":"2012","journal-title":"Immunity"},{"issue":"7","key":"2023012312514680200_jlb10509-bib-0020","doi-asserted-by":"crossref","first-page":"3549","DOI":"10.4049\/jimmunol.165.7.3549","article-title":"Defective NK cell activation in X-linked lymphoproliferative disease","volume":"165","author":"Benoit","year":"2000","journal-title":"J Immunol"},{"issue":"3","key":"2023012312514680200_jlb10509-bib-0021","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1084\/jem.194.3.235","article-title":"NTB-A [correction of GNTB-A], a novel SH2D1A-associated surface molecule contributing to the inability of natural killer cells to kill Epstein-Barr virus-infected B cells in X-linked lymphoproliferative disease","volume":"194","author":"Bottino","year":"2001","journal-title":"J Exp Med"},{"issue":"3","key":"2023012312514680200_jlb10509-bib-0022","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1084\/jem.192.3.337","article-title":"X-linked lymphoproliferative disease. 2B4 molecules displaying inhibitory rather than activating function are responsible for the inability of natural killer cells to kill Epstein-Barr virus-infected cells","volume":"192","author":"Parolini","year":"2000","journal-title":"J Exp Med"},{"issue":"2","key":"2023012312514680200_jlb10509-bib-0023","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.immuni.2016.07.013","article-title":"The self-specific activation receptor SLAM family is critical for NK cell education","volume":"45","author":"Chen","year":"2016","journal-title":"Immunity"},{"issue":"12","key":"2023012312514680200_jlb10509-bib-0024","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.it.2013.07.005","article-title":"Location and cellular stages of natural killer cell development","volume":"34","author":"Yu","year":"2013","journal-title":"Trends Immunol"},{"key":"2023012312514680200_jlb10509-bib-0025","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1146\/annurev.immunol.24.021605.090700","article-title":"Natural killer cell developmental pathways: a question of balance","volume":"24","author":"Di Santo","year":"2006","journal-title":"Annu Rev Immunol"},{"key":"2023012312514680200_jlb10509-bib-0026","doi-asserted-by":"crossref","first-page":"930","DOI":"10.3389\/fimmu.2017.00930","article-title":"Developmental and functional control of natural killer cells by cytokines","volume":"8","author":"Wu","year":"2017","journal-title":"Front Immunol"},{"issue":"12","key":"2023012312514680200_jlb10509-bib-0027","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1038\/ni1524","article-title":"NKG2D signaling is coupled to the interleukin 15 receptor signaling pathway","volume":"8","author":"Horng","year":"2007","journal-title":"Nat Immunol"},{"issue":"10","key":"2023012312514680200_jlb10509-bib-0028","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.1084\/jem.20160552","article-title":"Deletion of Slam locus in mice reveals inhibitory role of SLAM family in NK cell responses regulated by cytokines and LFA-1","volume":"213","author":"Guo","year":"2016","journal-title":"J Exp Med"},{"issue":"1","key":"2023012312514680200_jlb10509-bib-0029","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.immuni.2011.11.016","article-title":"The transcription factors T-bet and Eomes control key checkpoints of natural killer cell maturation","volume":"36","author":"Gordon","year":"2012","journal-title":"Immunity"},{"issue":"5","key":"2023012312514680200_jlb10509-bib-0030","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/S1074-7613(00)80664-0","article-title":"IL-15 receptor maintains lymphoid homeostasis by supporting lymphocyte homing and proliferation","volume":"9","author":"Lodolce","year":"1998","journal-title":"Immunity"}],"updated-by":[{"DOI":"10.1002\/jlb.10766","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2020,8,3]],"date-time":"2020-08-03T00:00:00Z","timestamp":1596412800000}}],"container-title":["Journal of Leukocyte Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/JLB.1MA1019-186R","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/JLB.1MA1019-186R","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/107\/4\/561\/48795914\/jlb10509.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/107\/4\/561\/48795914\/jlb10509.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T13:10:59Z","timestamp":1677503459000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jleukbio\/article\/107\/4\/561\/6884265"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,15]]},"references-count":30,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2019,11,15]]},"published-print":{"date-parts":[[2020,4,1]]}},"URL":"https:\/\/doi.org\/10.1002\/jlb.1ma1019-186r","relation":{"erratum":[{"id-type":"doi","id":"10.1002\/jlb.10766","asserted-by":"object"}]},"ISSN":["1938-3673","0741-5400"],"issn-type":[{"value":"1938-3673","type":"electronic"},{"value":"0741-5400","type":"print"}],"subject":[],"published-other":{"date-parts":[[2020,4]]},"published":{"date-parts":[[2019,11,15]]},"assertion":[{"value":"2019-07-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-10-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-11-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}