{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T09:14:14Z","timestamp":1762161254207,"version":"build-2065373602"},"reference-count":84,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2017,2,25]],"date-time":"2017-02-25T00:00:00Z","timestamp":1487980800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lysosomal storage diseases (LSDs) are inherited metabolic disorders characterized by the accumulation of different types of substrates in the lysosome. With a multisystemic involvement, LSDs often present a very broad clinical spectrum. In many LSDs, alterations of the immune system were described. Special emphasis was given to Natural Killer T (NKT) cells, a population of lipid-specific T cells that is activated by lipid antigens bound to CD1d (cluster of differentiation 1 d) molecules at the surface of antigen-presenting cells. These cells have important functions in cancer, infection, and autoimmunity and were altered in a variety of LSDs\u2019 mouse models. In some cases, the observed decrease was attributed to defects in either lipid antigen availability, trafficking, processing, or loading in CD1d. Here, we review the current knowledge about NKT cells in the context of LSDs, including the alterations detected, the proposed mechanisms to explain these defects, and the relevance of these findings for disease pathology. Furthermore, the effect of enzyme replacement therapy on NKT cells is also discussed.<\/jats:p>","DOI":"10.3390\/ijms18030502","type":"journal-article","created":{"date-parts":[[2017,2,27]],"date-time":"2017-02-27T11:00:20Z","timestamp":1488193220000},"page":"502","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["From Lysosomal Storage Diseases to NKT Cell Activation and Back"],"prefix":"10.3390","volume":"18","author":[{"given":"C\u00e1tia","family":"Pereira","sequence":"first","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal"},{"name":"IBMC\u2013Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal"}]},{"given":"Helena","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal"},{"name":"IBMC\u2013Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal"},{"name":"Departamento de Qu\u00edmica, Universidade de Aveiro, Campus Universit\u00e1rio de Santiago, 3810-193 Aveiro, Portugal"}]},{"given":"M.","family":"Macedo","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal"},{"name":"IBMC\u2013Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal"},{"name":"Departamento de Ci\u00eancias M\u00e9dicas, Universidade de Aveiro, Campus Universit\u00e1rio de Santiago Agra do crasto-edif\u00edcio 30, 3810-193 Aveiro, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2017,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1042\/bj0600604","article-title":"Tissue fractionation studies. 6. Intracellular distribution patterns of enzymes in rat-liver tissue","volume":"60","author":"Pressman","year":"1955","journal-title":"Biochem. J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1002\/iub.1288","article-title":"Impairment of homeostasis in lysosomal storage disorders","volume":"66","author":"Segatori","year":"2014","journal-title":"IUBMB Life"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1146\/annurev-med-122313-085916","article-title":"Lysosomal storage diseases: From pathophysiology to therapy","volume":"66","author":"Parenti","year":"2015","journal-title":"Ann. Rev. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1134\/S0006297914070049","article-title":"Secondary biochemical and morphological consequences in lysosomal storage diseases","volume":"79","author":"Alroy","year":"2014","journal-title":"Biochem. Moscow"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1146\/annurev-immunol-032414-112008","article-title":"The immunology of CD1- and MR1-restricted T cells","volume":"34","author":"Mori","year":"2016","journal-title":"Ann. Rev. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/nri1309","article-title":"NKT cells: What\u2019s in a name?","volume":"4","author":"Godfrey","year":"2004","journal-title":"Nat. Rev. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1111\/imm.12247","article-title":"Different subsets of natural killer T cells may vary in their roles in health and disease","volume":"142","author":"Kumar","year":"2014","journal-title":"Immunology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1007\/s00251-016-0944-8","article-title":"Activation strategies for invariant natural killer T cells","volume":"68","author":"Kohlgruber","year":"2016","journal-title":"Immunogenetics"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1111\/j.1365-3083.2012.02750.x","article-title":"Immunomodulatory type II natural killer T lymphocytes in health and disease","volume":"76","author":"Rhost","year":"2012","journal-title":"Scand. J. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"316","DOI":"10.3389\/fimmu.2015.00316","article-title":"Type II NKT cells in inflammation, autoimmunity, microbial immunity, and cancer","volume":"6","author":"Marrero","year":"2015","journal-title":"Front. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2851","DOI":"10.1002\/eji.201142350","article-title":"Identification of novel glycolipid ligands activating a sulfatide-reactive, CD1d-restricted, type II natural killer T lymphocyte","volume":"42","author":"Rhost","year":"2012","journal-title":"Eur. J. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4580","DOI":"10.4049\/jimmunol.1400699","article-title":"Recognition of lysophosphatidylcholine by type II NKT cells and protection from an inflammatory liver disease","volume":"193","author":"Maricic","year":"2014","journal-title":"J. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1182\/blood-2014-09-600270","article-title":"Type II NKT-TFH cells against gaucher lipids regulate B cell immunity and inflammation","volume":"125","author":"Nair","year":"2014","journal-title":"Blood"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2876275","DOI":"10.1155\/2016\/2876275","article-title":"CD1-restricted T cells at the crossroad of innate and adaptive immunity","volume":"2016","author":"Pereira","year":"2016","journal-title":"J. Immunol. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1084\/jem.20031389","article-title":"Prevention of autoimmunity by targeting a distinct, noninvariant CD1d-reactive T cell population reactive to sulfatide","volume":"199","author":"Jahng","year":"2004","journal-title":"J. Exp. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"10984","DOI":"10.1073\/pnas.1000576107","article-title":"Oligoclonality and innate-like features in the TCR repertoire of type II NKT cells reactive to a \u03b2-linked self-glycolipid","volume":"107","author":"Arrenberg","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1365-2567.2007.02647.x","article-title":"Characterization of human invariant natural killer t subsets in health and disease using a novel invariant natural killer T cell-clonotypic monoclonal antibody, 6b11","volume":"122","author":"Montoya","year":"2007","journal-title":"Immunology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1084\/jem.20011786","article-title":"Functionally distinct subsets of CD1d-restricted natural killer T cells revealed by CD1d tetramer staining","volume":"195","author":"Gumperz","year":"2002","journal-title":"J. Exp. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/nri2904","article-title":"Presumed guilty: Natural killer T cell defects and human disease","volume":"11","author":"Berzins","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1002\/eji.200939349","article-title":"Invariant NKT cells and CD1d+ cells amass in human omentum and are depleted in patients with cancer and obesity","volume":"39","author":"Lynch","year":"2009","journal-title":"Eur. J. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/j.immuni.2012.06.016","article-title":"Adipose tissue invariant NKT cells protect against diet-induced obesity and metabolic disorder through regulatory cytokine production","volume":"37","author":"Lynch","year":"2012","journal-title":"Immunity"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3343","DOI":"10.1172\/JCI62739","article-title":"Natural killer T cells in adipose tissue prevent insulin resistance","volume":"122","author":"Schipper","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"E1143","DOI":"10.1073\/pnas.1200498109","article-title":"Activation of invariant natural killer T cells by lipid excess promotes tissue inflammation, insulin resistance, and hepatic steatosis in obese mice","volume":"109","author":"Wu","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/ni.3047","article-title":"Regulatory inkt cells lack expression of the transcription factor PLZF and control the homeostasis of Treg cells and macrophages in adipose tissue","volume":"16","author":"Lynch","year":"2015","journal-title":"Nat. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1016\/j.cmet.2016.08.003","article-title":"iNKT cells induce FGF21 for thermogenesis and are required for maximal weight loss in GLP1 therapy","volume":"24","author":"Lynch","year":"2016","journal-title":"Cell Metab."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"28473","DOI":"10.1038\/srep28473","article-title":"Adipocyte-specific CD1d-deficiency mitigates diet-induced obesity and insulin resistance in mice","volume":"6","author":"Satoh","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1146\/annurev-immunol-032713-120243","article-title":"Biology of CD1- and MR1-restricted T cells","volume":"32","author":"Salio","year":"2014","journal-title":"Ann. Rev. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/ni.1841","article-title":"Raising the NKT cell family","volume":"11","author":"Godfrey","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1084\/jem.20011908","article-title":"Distinct functional lineages of human V\u03b124 natural killer T cells","volume":"195","author":"Lee","year":"2002","journal-title":"J. Exp. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3140","DOI":"10.4049\/jimmunol.168.7.3140","article-title":"Cutting edge: Analysis of human V\u03b124+CD8+ NK T cells activated by \u03b1-galactosylceramide-pulsed monocyte-derived dendritic cells","volume":"168","author":"Takahashi","year":"2002","journal-title":"J. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"O\u2019Reilly, V., Zeng, S.G., Bricard, G., Atzberger, A., Hogan, A.E., Jackson, J., Feighery, C., Porcelli, S.A., and Doherty, D.G. (2011). Distinct and overlapping effector functions of expanded human CD4+, CD8ALPHA+ and CD4\u2212CD8\u0391\u2212 invariant natural killer T cells. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0028648"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5758","DOI":"10.4049\/jimmunol.1003043","article-title":"Proinflammatory environment dictates the IL-17-producing capacity of human invariant NKT cells","volume":"186","author":"Resende","year":"2011","journal-title":"J. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"805","DOI":"10.4049\/jimmunol.1201010","article-title":"Induced IL-17-producing invariant NKT cells require activation in presence of TGF-\u03b2 and IL-1\u03b2","volume":"190","author":"Monteiro","year":"2013","journal-title":"J. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3463","DOI":"10.4049\/jimmunol.1403170","article-title":"IL-9 expression by invariant NKT cells is not imprinted during thymic development","volume":"195","author":"Monteiro","year":"2015","journal-title":"J. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1084\/jem.182.4.993","article-title":"CD1-restricted CD4+ T cells in major histocompatibility complex class II-deficient mice","volume":"182","author":"Cardell","year":"1995","journal-title":"J. Exp. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1084\/jem.193.8.893","article-title":"The mouse cd1d-restricted repertoire is dominated by a few autoreactive T cell receptor families","volume":"193","author":"Park","year":"2001","journal-title":"J. Exp. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5531","DOI":"10.4049\/jimmunol.167.10.5531","article-title":"A major fraction of human bone marrow lymphocytes are Th2-like CD1d-reactive T cells that can suppress mixed lymphocyte responses","volume":"167","author":"Exley","year":"2001","journal-title":"J. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.4049\/jimmunol.168.4.1519","article-title":"Cutting edge: Compartmentalization of Th1-like noninvariant CD1d-reactive T cells in hepatitis c virus-infected liver","volume":"168","author":"Exley","year":"2002","journal-title":"J. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1182\/blood-2008-04-149831","article-title":"Inflammation-associated lysophospholipids as ligands for CD1D-restricted T cells in human cancer","volume":"112","author":"Chang","year":"2008","journal-title":"Blood"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2505","DOI":"10.1002\/eji.201242531","article-title":"The majority of CD1D-sulfatide-specific T cells in human blood use a semiinvariant V\u03941 TCR","volume":"42","author":"Bai","year":"2012","journal-title":"Eur. J. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1126\/science.291.5504.664","article-title":"Glycolipid antigen processing for presentation by CD1d molecules","volume":"291","author":"Prigozy","year":"2001","journal-title":"Science"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1038\/ni.2096","article-title":"Invariant natural killer T cells recognize glycolipids from pathogenic gram-positive bacteria","volume":"12","author":"Kinjo","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1126\/science.1103440","article-title":"Lysosomal glycosphingolipid recognition by NKT cells","volume":"306","author":"Zhou","year":"2004","journal-title":"Science"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Fox, L.M., Cox, D.G., Lockridge, J.L., Wang, X., Chen, X., Scharf, L., Trott, D.L., Ndonye, R.M., Veerapen, N., and Besra, G.S. (2009). Recognition of lyso-phospholipids by human natural killer T lymphocytes. PLoS Biol., 7.","DOI":"10.1371\/journal.pbio.1000228"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5097","DOI":"10.1073\/pnas.1302923110","article-title":"Role for lysosomal phospholipase A2 in iNKT cell-mediated CD1d recognition","volume":"110","author":"Paduraru","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.immuni.2014.08.017","article-title":"The identification of the endogenous ligands of natural killer T cells reveals the presence of mammalian \u03b1-linked glycosylceramides","volume":"41","author":"Kain","year":"2014","journal-title":"Immunity"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/ni1034","article-title":"Saposins facilitate CD1D-restricted presentation of an exogenous lipid antigen to T cells","volume":"5","author":"Kang","year":"2004","journal-title":"Nat. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1126\/science.1092009","article-title":"Editing of CD1d-bound lipid antigens by endosomal lipid transfer proteins","volume":"303","author":"Zhou","year":"2004","journal-title":"Science"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"5551","DOI":"10.1073\/pnas.0700617104","article-title":"Saposin b is the dominant saposin that facilitates lipid binding to human CD1d molecules","volume":"104","author":"Yuan","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"E4753","DOI":"10.1073\/pnas.1310050110","article-title":"Saposins modulate human invariant natural killer T cells self-reactivity and facilitate lipid exchange with CD1d molecules during antigen presentation","volume":"110","author":"Salio","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1084\/jem.20061562","article-title":"The niemann-pick type C2 protein loads isoglobotrihexosylceramide onto CD1d molecules and contributes to the thymic selection of NKT cells","volume":"204","author":"Schrantz","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1126\/science.1115301","article-title":"Assistance of microbial glycolipid antigen processing by CD1e","volume":"310","author":"Mariotti","year":"2005","journal-title":"Science"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"14228","DOI":"10.1073\/pnas.1108809108","article-title":"Fine tuning by human CD1e of lipid-specific immune responses","volume":"108","author":"Facciotti","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.it.2012.01.005","article-title":"Novel insights into lipid antigen presentation","volume":"33","author":"Mori","year":"2012","journal-title":"Trends Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1084\/jem.189.1.103","article-title":"Distinct subsets of cd1d-restricted T cells recognize self-antigens loaded in different cellular compartments","volume":"189","author":"Chiu","year":"1999","journal-title":"J. Exp. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/ni740","article-title":"Multiple defects in antigen presentation and T cell development by mice expressing cytoplasmic tail-truncated CD1d","volume":"3","author":"Chiu","year":"2002","journal-title":"Nat. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"6181","DOI":"10.4049\/jimmunol.178.10.6181","article-title":"Distinct endosomal trafficking requirements for presentation of autoantigens and exogenous lipids by human CD1d molecules","volume":"178","author":"Chen","year":"2007","journal-title":"J. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"E5678","DOI":"10.1073\/pnas.1413935112","article-title":"Essential role for autophagy during invariant NKT cell development","volume":"111","author":"Salio","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"5872","DOI":"10.4049\/jimmunol.1402154","article-title":"Invariant nkt cells require autophagy to coordinate proliferation and survival signals during differentiation","volume":"194","author":"Pei","year":"2015","journal-title":"J. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1002\/eji.200737160","article-title":"Differential alteration of lipid antigen presentation to NKT cells due to imbalances in lipid metabolism","volume":"37","author":"Schumann","year":"2007","journal-title":"Eur. J. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2293","DOI":"10.1084\/jem.20060921","article-title":"Impaired selection of invariant natural killer T cells in diverse mouse models of glycosphingolipid lysosomal storage diseases","volume":"203","author":"Gadola","year":"2006","journal-title":"J. Exp. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"26","DOI":"10.4049\/jimmunol.177.1.26","article-title":"Cutting edge: Impaired glycosphingolipid trafficking and NKT cell development in mice lacking niemann-pick type c1 protein","volume":"177","author":"Sagiv","year":"2006","journal-title":"J. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.immuni.2010.08.003","article-title":"Lysosomal \u03b1-galactosidase controls the generation of self lipid antigens for natural killer T cells","volume":"33","author":"Darmoise","year":"2010","journal-title":"Immunity"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.ymgme.2012.02.014","article-title":"Enzyme replacement therapy partially prevents invariant natural killer T cell deficiency in the fabry disease mouse model","volume":"106","author":"Macedo","year":"2012","journal-title":"Mol. Genet. Metab."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3007","DOI":"10.4049\/jimmunol.1201483","article-title":"Globosides but not isoglobosides can impact the development of invariant NKT cells and their interaction with dendritic cells","volume":"189","author":"Porubsky","year":"2012","journal-title":"J. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2748","DOI":"10.1002\/eji.200939639","article-title":"Development and maturation of invariant NKT cells in the presence of lysosomal engulfment","volume":"39","author":"Plati","year":"2009","journal-title":"Eur. J. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1111\/j.1365-2141.2005.05503.x","article-title":"Evidence for a link between sphingolipid metabolism and expression of CD1d and MHC-class II: Monocytes from gaucher disease patients as a model","volume":"129","author":"Balreira","year":"2005","journal-title":"Br. J. Haematol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1111\/j.1365-2141.2008.07380.x","article-title":"Anomalies in conventional T and invariant natural killer T-cell populations in fabry mice but not in fabry patients","volume":"143","author":"Balreira","year":"2008","journal-title":"Br. J. Haematol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"S67","DOI":"10.1007\/s10545-009-1060-9","article-title":"Leukocyte perturbation associated with fabry disease","volume":"32","author":"Rozenfeld","year":"2009","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1886","DOI":"10.1002\/eji.201141821","article-title":"Invariant natural killer T cells are not affected by lysosomal storage in patients with niemann-pick disease type c","volume":"42","author":"Speak","year":"2012","journal-title":"Eur. J. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.ymgme.2013.01.018","article-title":"Invariant natural killer T cells are phenotypically and functionally altered in fabry disease","volume":"108","author":"Pereira","year":"2013","journal-title":"Mol. Genet. Metab."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1111\/imr.12431","article-title":"The processing and presentation of lipids and glycolipids to the immune system","volume":"272","author":"Vartabedian","year":"2016","journal-title":"Immunol. Rev."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1002\/eji.200425958","article-title":"Limited correlation between human thymus and blood NKT cell content revealed by an ontogeny study of paired tissue samples","volume":"35","author":"Berzins","year":"2005","journal-title":"Eur. J. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.bbadis.2011.11.001","article-title":"Globotriaosylceramide is correlated with oxidative stress and inflammation in fabry patients treated with enzyme replacement therapy","volume":"1822","author":"Biancini","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1172\/JCI117084","article-title":"Marked elevation of plasma chitotriosidase activity. A novel hallmark of gaucher disease","volume":"93","author":"Hollak","year":"1994","journal-title":"J. Clin.Investig."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1038\/ni.2245","article-title":"Peroxisome-derived lipids are self antigens that stimulate invariant natural killer T cells in the thymus","volume":"13","author":"Facciotti","year":"2012","journal-title":"Nat. Immunol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1002\/eji.201545725","article-title":"Globotriaosylceramide inhibits iNKT-cell activation in a CD1d-dependent manner","volume":"46","author":"Pereira","year":"2016","journal-title":"Eur. J. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.beem.2014.08.005","article-title":"Non-neuronopathic lysosomal storage disorders: Disease spectrum and treatments","volume":"29","author":"Pastores","year":"2015","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1177\/1060028013500469","article-title":"Gaucher disease and its treatment options","volume":"47","author":"Bennett","year":"2013","journal-title":"Ann. Pharmacother."},{"key":"ref_80","unstructured":"Valle, D., Beaudet, A.L., Vogelstein, B., Kinzler, K.W., Antonarakis, S.E., Ballabio, A., Gibson, K.M., and Mitchell, G. (2013). The Online Metabolic and Molecular Bases of Inherited Disease, McGraw-Hill Medical."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.beem.2014.08.006","article-title":"The attenuated\/late onset lysosomal storage disorders: Therapeutic goals and indications for enzyme replacement treatment in gaucher and fabry disease","volume":"29","author":"Hollak","year":"2015","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"150450","DOI":"10.1155\/2011\/150450","article-title":"Gaucher disease and cancer: Concept and controversy","volume":"2011","author":"Choy","year":"2011","journal-title":"Int. J. Cell Biol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"20423","DOI":"10.1074\/jbc.R110.134452","article-title":"Common and uncommon pathogenic cascades in lysosomal storage diseases","volume":"285","author":"Vitner","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/1742-2094-7-39","article-title":"Mucopolysaccharidosis IIIb, a lysosomal storage disease, triggers a pathogenic CNS autoimmune response","volume":"7","author":"Killedar","year":"2010","journal-title":"J. Neuroinflamm."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/3\/502\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:29:12Z","timestamp":1760207352000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/3\/502"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,2,25]]},"references-count":84,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2017,3]]}},"alternative-id":["ijms18030502"],"URL":"https:\/\/doi.org\/10.3390\/ijms18030502","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2017,2,25]]}}}