{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:33:04Z","timestamp":1790173984570,"version":"4.1.0"},"reference-count":58,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,5,5]],"date-time":"2017-05-05T00:00:00Z","timestamp":1493942400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004963","name":"Seventh Framework Programme","doi-asserted-by":"publisher","award":["306124"],"award-info":[{"award-number":["306124"]}],"id":[{"id":"10.13039\/501100004963","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["5xmille 2013 (HSM)"],"award-info":[{"award-number":["5xmille 2013 (HSM)"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["RF\u20102010\u20102316606"],"award-info":[{"award-number":["RF\u20102010\u20102316606"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["RF\u2010TOS\u20102008\u20101219488"],"award-info":[{"award-number":["RF\u2010TOS\u20102008\u20101219488"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["5x1000\u20109962"],"award-info":[{"award-number":["5x1000\u20109962"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["IG\u201010225"],"award-info":[{"award-number":["IG\u201010225"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["IG\u201010643"],"award-info":[{"award-number":["IG\u201010643"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["IG\u201016764"],"award-info":[{"award-number":["IG\u201016764"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:p>X\u2010linked lymphoproliferative disease 1 (XLP1) is an inherited immunodeficiency, caused by mutations in <jats:italic>SH2D1A<\/jats:italic> encoding Signaling Lymphocyte Activation Molecule (SLAM)\u2010associated protein (SAP). In XLP1, 2B4, upon engagement with CD48, has inhibitory instead of activating function. This causes a selective inability of cytotoxic effectors to kill EBV\u2010infected cells, with dramatic clinical sequelae. Here, we investigated the NK cell education in XLP1, upon characterization of killer Ig\u2010like receptor (KIR)\/KIR\u2010L genotype and phenotypic repertoire of self\u2010HLA class I specific inhibitory NK receptors (self\u2010iNKRs). We also analyzed NK\u2010cell cytotoxicity against CD48<jats:sup>+<\/jats:sup> or CD48<jats:sup>\u2212<\/jats:sup> KIR\u2010ligand matched or autologous hematopoietic cells in XLP1 patients and healthy controls. XLP1 NK cells may show a defective phenotypic repertoire with substantial proportion of cells lacking self\u2010iNKR. These NK cells are cytotoxic and the inhibitory 2B4\/CD48 pathway plays a major role to prevent killing of CD48<jats:sup>+<\/jats:sup> EBV\u2010transformed B cells and M1 macrophages. Importantly, self\u2010iNKR defective NK cells kill CD48<jats:sup>\u2212<\/jats:sup> targets, such as mature DCs. Self\u2010iNKR<jats:sup>\u2212<\/jats:sup> NK cells in XLP1 patients are functional even in resting conditions, suggesting a role of the inhibitory 2B4\/CD48 pathway in the education process during NK\u2010cell maturation. Killing of autologous mature DC by self\u2010iNKR defective XLP1 NK cells may impair adaptive responses, further exacerbating the patients\u2019 immune defect.<\/jats:p>","DOI":"10.1002\/eji.201646885","type":"journal-article","created":{"date-parts":[[2017,4,7]],"date-time":"2017-04-07T04:23:06Z","timestamp":1491538986000},"page":"1051-1061","source":"Crossref","is-referenced-by-count":19,"title":["Inhibitory 2B4 contributes to NK cell education and immunological derangements in XLP1 patients"],"prefix":"10.1002","volume":"47","author":[{"given":"Raffaella","family":"Meazza","sequence":"first","affiliation":[{"name":"Dipartimento delle Terapie Oncologiche Integrate IRCCS AOU San Martino\u2010IST  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Falco","sequence":"additional","affiliation":[{"name":"Dipartimento di Ricerca e Diagnostica IRCCS Istituto Giannina Gaslini  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Marcenaro","sequence":"additional","affiliation":[{"name":"Dipartimento di Ricerca e Diagnostica IRCCS Istituto Giannina Gaslini  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Loiacono","sequence":"additional","affiliation":[{"name":"Dipartimento delle Terapie Oncologiche Integrate IRCCS AOU San Martino\u2010IST  Genoa Italy"},{"name":"Dipartimento di Ricerca e Diagnostica IRCCS Istituto Giannina Gaslini  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Canevali","sequence":"additional","affiliation":[{"name":"Dipartimento di Ricerca e Diagnostica IRCCS Istituto Giannina Gaslini  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Bellora","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Sperimentale Universit\u00e0 degli Studi di Genova  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Tuberosa","sequence":"additional","affiliation":[{"name":"Dipartimento delle Terapie Oncologiche Integrate IRCCS AOU San Martino\u2010IST  Genoa Italy"},{"name":"Dipartimento di Medicina Sperimentale Universit\u00e0 degli Studi di Genova  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Locatelli","sequence":"additional","affiliation":[{"name":"Dipartimento di Oncoematologia Pediatrica IRCCS Ospedale Bambino Ges\u00f9  Rome Italy"},{"name":"Universit\u00e0 di Pavia  Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Concetta","family":"Micalizzi","sequence":"additional","affiliation":[{"name":"Dipartimento di Oncoematologia Pediatrica IRCCS Istituto Giannina Gaslini  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Moretta","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Sperimentale Universit\u00e0 degli Studi di Genova  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria C.","family":"Mingari","sequence":"additional","affiliation":[{"name":"Dipartimento delle Terapie Oncologiche Integrate IRCCS AOU San Martino\u2010IST  Genoa Italy"},{"name":"Dipartimento di Medicina Sperimentale Universit\u00e0 degli Studi di Genova  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Moretta","sequence":"additional","affiliation":[{"name":"Dipartimento dei Laboratori Area di Ricerca di Immunologia IRCCS Ospedale Bambino Ges\u00f9  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Aric\u00f2","sequence":"additional","affiliation":[{"name":"Azienda Sanitaria Provinciale  Ragusa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Bottino","sequence":"additional","affiliation":[{"name":"Dipartimento di Ricerca e Diagnostica IRCCS Istituto Giannina Gaslini  Genoa Italy"},{"name":"Dipartimento di Medicina Sperimentale Universit\u00e0 degli Studi di Genova  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1565-451X","authenticated-orcid":false,"given":"Daniela","family":"Pende","sequence":"additional","affiliation":[{"name":"Dipartimento delle Terapie Oncologiche Integrate IRCCS AOU San Martino\u2010IST  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,5,5]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.21039"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-014-0083-7"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-06-284935"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-07-298372"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/2424"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/26683"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-030409-101302"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.3.235"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200424886"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.160010"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2015.11.003"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.3.337"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2014.04.043"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.19.1.197"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201344312"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201444562"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2005.02.007"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600019"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2008.03.005"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1863"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.23.021704.115526"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.20.092501.134942"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.6.3969"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-06-164103"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00184"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12316"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03847"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2006.06.013"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.08.031"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-03-143727"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2011.06.001"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.12.6640"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201546236"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2006.00450.x"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200323986"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3369"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200939307"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.072065999"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20030305"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-04-017343"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-09-238832"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1763"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0153236"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.07.013"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.07.020"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a007229"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004000"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/11360"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.6.3690"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001187"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.137976.112"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/tan.12299"},{"key":"e_1_2_7_54_1","first-page":"197","article-title":"Hemophagocytic lymphohistiocytosis. Report of 122 children from the International Registry. FHL study group of the Histiocyte society","volume":"10","author":"Arico M.","year":"1996","journal-title":"Leukemia"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903632"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-04-015693"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-07-2696"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1007654108"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-08-374199"}],"container-title":["European Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Feji.201646885","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/eji.201646885","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T20:08:12Z","timestamp":1695672492000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/eji.201646885"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5,5]]},"references-count":58,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2017,6]]}},"alternative-id":["10.1002\/eji.201646885"],"URL":"https:\/\/doi.org\/10.1002\/eji.201646885","archive":["Portico"],"relation":{},"ISSN":["0014-2980","1521-4141"],"issn-type":[{"value":"0014-2980","type":"print"},{"value":"1521-4141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,5,5]]}}}