{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T10:34:19Z","timestamp":1768473259196,"version":"3.49.0"},"reference-count":17,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,10,20]],"date-time":"2015-10-20T00:00:00Z","timestamp":1445299200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:p>Globotriaosylceramide (Gb3) is a glycosphingolipid present in cellular membranes that progressively accumulates in Fabry disease. Invariant Natural Killer T (iNKT) cells are a population of lipid\u2010specific T cells that are phenotypically and functionally altered in Fabry disease. The mechanisms responsible for the iNKT\u2010cell alterations in Fabry disease are not well understood. Here, we analyzed the effect of Gb3 on CD1d\u2010mediated iNKT\u2010cell activation in vitro using human cells and in vivo in the mouse model. We found that Gb3 competes with endogenous and exogenous antigens for CD1d binding, thereby reducing the activation of iNKT cells. This effect was exerted by a reduction in the amount of stimulatory CD1d:\u03b1\u2013GalCer complexes in the presence of Gb3 as demonstrated by using an mAb specific for the complex. We also found that administration of Gb3 delivered to the same APC as \u03b1\u2010GalCer, induces reduced iNKT\u2010cell activation in vivo. This work highlights the complexity of iNKT\u2010cell activation and the importance of nonantigenic glycosphingolipids in the modulation of this process.<\/jats:p>","DOI":"10.1002\/eji.201545725","type":"journal-article","created":{"date-parts":[[2015,10,1]],"date-time":"2015-10-01T22:50:58Z","timestamp":1443739858000},"page":"147-153","source":"Crossref","is-referenced-by-count":17,"title":["Globotriaosylceramide inhibits iNKT\u2010cell activation in a CD1d\u2010dependent manner"],"prefix":"10.1002","volume":"46","author":[{"given":"Catia S.","family":"Pereira","sequence":"first","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade Universidade do Porto  Portugal"},{"name":"Lysosome and Peroxisome Biology Unit (UniLiPe) IBMC \u2013 Instituto de Biologia Molecular e Celular Universidade do Porto  Porto Portugal"},{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar (ICBAS) Universidade do Porto  Porto Portugal"}]},{"given":"Clara","family":"Sa\u2010Miranda","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade Universidade do Porto  Portugal"},{"name":"Lysosome and Peroxisome Biology Unit (UniLiPe) IBMC \u2013 Instituto de Biologia Molecular e Celular Universidade do Porto  Porto Portugal"}]},{"given":"Gennaro","family":"De Libero","sequence":"additional","affiliation":[{"name":"Singapore Immunology Network Agency for Science Technology and Research  Singapore Singapore"},{"name":"Experimental Immunology Department of Biomedicine University of Basel  Basel Switzerland"}]},{"given":"Lucia","family":"Mori","sequence":"additional","affiliation":[{"name":"Singapore Immunology Network Agency for Science Technology and Research  Singapore Singapore"},{"name":"Experimental Immunology Department of Biomedicine University of Basel  Basel Switzerland"}]},{"given":"Maria Fatima","family":"Macedo","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade Universidade do Porto  Portugal"},{"name":"Lysosome and Peroxisome Biology Unit (UniLiPe) IBMC \u2013 Instituto de Biologia Molecular e Celular Universidade do Porto  Porto Portugal"},{"name":"Aveiro Health Sciences Program University of Aveiro  Aveiro Portugal"}]}],"member":"311","published-online":{"date-parts":[[2015,10,20]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-009-1060-9"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2012.08.003"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.291.5504.664"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20060921"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2008.07380.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2012.02.014"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1841"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.08.017"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2013.01.018"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.08.003"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1201483"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1103440"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/cb800277n"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2076"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200737160"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxr108"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.308783"}],"container-title":["European 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