{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:43:30Z","timestamp":1791265410004,"version":"4.1.0"},"reference-count":37,"publisher":"National Academy of Sciences","issue":"14","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,4,3]]},"abstract":"<jats:p>\n                    CD1d-restricted natural killer T (NKT) cells, expressing the invariant T cell antigen receptor (TCR) chain encoded by V\u03b114-J\u03b118 gene segments in mice and V\u03b124-J\u03b118 in humans [invariant NKT (iNKT) cells], contribute to immunoregulatory processes, such as tolerance, host defense, and tumor surveillance. iNKT cells are positively selected in the thymus by CD1d molecules expressed by CD4\n                    <jats:sup>+<\/jats:sup>\n                    \/CD8\n                    <jats:sup>+<\/jats:sup>\n                    cortical thymocytes. However, the identity of the endogenous lipid(s) responsible for positive selection of iNKT cells remains unclear. One candidate lipid proposed to play a role in positive selection is isoglobotrihexosylceramide (iGb3). However, no direct evidence for its physiological role has been provided. Therefore, to directly investigate the role of iGb3 in iNKT cell selection, we have generated mice deficient in iGb3 synthase [\n                    <jats:italic>iGb3S<\/jats:italic>\n                    , also known as \u03b11\u20133galactosyltransferase 2 (\n                    <jats:italic>A3galt2<\/jats:italic>\n                    )]. These mice developed, grew, and reproduced normally and exhibited no overt behavioral abnormalities. Consistent with the notion that iGb3 is synthesized only by\n                    <jats:italic>iGb3S<\/jats:italic>\n                    , lack of iGb3 in the dorsal root ganglia of\n                    <jats:italic>iGb3S<\/jats:italic>\n                    -deficient mice (\n                    <jats:italic>iGb3S<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ), as compared with\n                    <jats:italic>iGb3S<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    mice, was confirmed.\n                    <jats:italic>iGb3S<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice showed normal numbers of iNKT cells in the thymus, spleen, and liver with selected TCR V\u03b2 chains identical to controls. Upon administration of \u03b1-galactosylceramide, activation of iNKT and dendritic cells was similar in\n                    <jats:italic>iGb3S<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    and\n                    <jats:italic>iGb3S<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    mice, as measured by up-regulation of CD69 as well as intracellular IL-4 and IFN-\u03b3 in iNKT cells, up-regulation of CD86 on dendritic cells, and rise in serum concentrations of IL-4, IL-6, IL-10, IL-12p70, IFN-\u03b3, TNF-\u03b1, and Ccl2\/MCP-1. Our results strongly suggest that iGb3 is unlikely to be an endogenous CD1d lipid ligand determining thymic iNKT selection.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0611139104","type":"journal-article","created":{"date-parts":[[2007,3,19]],"date-time":"2007-03-19T20:36:00Z","timestamp":1174336560000},"page":"5977-5982","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":198,"title":["Normal development and function of invariant natural killer T cells in mice with isoglobotrihexosylceramide (iGb3) deficiency"],"prefix":"10.1073","volume":"104","author":[{"given":"Stefan","family":"Porubsky","sequence":"first","affiliation":[{"name":"*Department of Cellular and Molecular Pathology, German Cancer Research Center, 69120 Heidelberg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anneliese O.","family":"Speak","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Oxford, Oxford OX1 3QT, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Luckow","sequence":"additional","affiliation":[{"name":"Medical Policlinic of the University of Munich, Division of Clinical Biochemistry, 80336 Munich, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Cerundolo","sequence":"additional","affiliation":[{"name":"Weatherall Institute of Molecular Medicine, Tumor Immunology Group, John Radcliffe Hospital, Oxford OX3 9DS, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances M.","family":"Platt","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Oxford, Oxford OX1 3QT, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann-Josef","family":"Gr\u00f6ne","sequence":"additional","affiliation":[{"name":"*Department of Cellular and Molecular Pathology, German Cancer Research Center, 69120 Heidelberg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2007,4,3]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(97)01065-2"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.22.012703.104608"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.17.1.297"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri854"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/7.7.1157"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.14.6506"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.180.3.1097"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5343.1626"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2003.09.007"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.21.120601.141057"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20060418"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.11.5409"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni740"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5302.977"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1092009"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni844"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0430327100"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1103440"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2006.01.040"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03408"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20060921"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.1.26"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20061787"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0607285104"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M002629200"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.14.7945"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/23.24.5080"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1069017"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.189.7.1121"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.5.741"},{"key":"e_1_3_4_31_2","doi-asserted-by":"crossref","first-page":"93","DOI":"10.4049\/jimmunol.163.1.93","volume":"163","author":"Tomura M","year":"1999","unstructured":"M Tomura, WG Yu, HJ Ahn, M Yamashita, YF Yang, S Ono, T Hamaoka, T Kawano, M Taniguchi, Y Koezuka, et al. J Immunol 163, 93\u2013101 (1999).","journal-title":"J Immunol"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni851"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.4.2448"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwg030"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(00)01757-6"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(87)90021-2"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.2.849-858.2005"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0611139104","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T23:20:58Z","timestamp":1683760858000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0611139104"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,4,3]]},"references-count":37,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2007,4,3]]}},"alternative-id":["10.1073\/pnas.0611139104"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0611139104","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,4,3]]},"assertion":[{"value":"2006-12-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2007-04-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}