title: Development and maturation of invariant NKT cells in the presence of lysosomal engulfment.
abstract: A defect in invariant NKT (iNKT) cell selection was hypothesized in lysosomal storage disorders (LSD). Accumulation of glycosphingolipids (GSL) in LSD could influence lipid loading and/or presentation causing entrapment of endogenous ligand(s) within storage bodies or competition of the selecting ligand(s) by stored lipids for CD1d binding. However, when we analyzed the iNKT cell compartment in newly tested LSD animal models that accumulate GSL, glycoaminoglycans or both, we observed a defective iNKT cell selection only in animals affected by multiple sulfatase deficiency, in which a generalized aberrant T-cell development, rather than a pure iNKT defect, was present. Mice with single lysosomal enzyme deficiencies had normal iNKT cell development. Thus, GSL/glycoaminoglycans storage and lysosomal engulfment are not sufficient for affecting iNKT cell development. Rather, lipid ligand(s) or storage compounds, which are affected in those LSD lacking mature iNKT cells, might indeed be relevant for iNKT cell selection.
authors.affiliation: San Raffaele Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Plati
authors.forename: Ilaria
authors.initials: I
authors.lastname: Visigalli
authors.forename: Alessia
authors.initials: A
authors.lastname: Capotondo
authors.forename: Mario
authors.initials: M
authors.lastname: Buono
authors.forename: Luigi
authors.initials: L
authors.lastname: Naldini
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Cosma
authors.forename: Alessandra
authors.initials: A
authors.lastname: Biffi
mesh_terms: D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007965:Leukodystrophy, Globoid Cell / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007966:Leukodystrophy, Metachromatic / Q000235:genetics / Q000276:immunology; D008099:Liver / Q000276:immunology / Q000473:pathology; D008214:Lymphocytes / Q000473:pathology; D016464:Lysosomal Storage Diseases / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008059:Mucopolysaccharidosis I / Q000235:genetics / Q000276:immunology; D052517:Multiple Sulfatase Deficiency Disease / Q000235:genetics / Q000276:immunology / Q000473:pathology; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000473:pathology; D011758:Pyrroles / Q000494:pharmacology; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000037:antagonists & inhibitors; D012497:Sandhoff Disease / Q000235:genetics / Q000276:immunology / Q000473:pathology; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013950:Thymus Gland / Q000276:immunology / Q000473:pathology
chemical_list: D004791:Enzyme Inhibitors; D011758:Pyrroles; C105686:SU 5402; D051496:Receptor, Fibroblast Growth Factor, Type 1