title: From Lysosomal Storage Diseases to NKT Cell Activation and Back.
abstract: 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' 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.
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal. cspereira@ibmc.up.pt.|IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal. cspereira@ibmc.up.pt.
authors.forename: Cátia S
authors.initials: CS
authors.lastname: Pereira
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal. helena.ribeiro@ibmc.up.pt.|IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal. helena.ribeiro@ibmc.up.pt.|Departamento de Química, Universidade de Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal. helena.ribeiro@ibmc.up.pt.
authors.forename: Helena
authors.initials: H
authors.lastname: Ribeiro
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal. fmacedo@ibmc.up.pt.|IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal. fmacedo@ibmc.up.pt.|Departamento de Ciências Médicas, Universidade de Aveiro, Campus Universitário de Santiago Agra do crasto-edifício 30, 3810-193 Aveiro, Portugal. fmacedo@ibmc.up.pt.
authors.forename: M Fatima
authors.initials: MF
authors.lastname: Macedo
mesh_terms: D000818:Animals; D055610:Antigens, CD1d / Q000378:metabolism; D056947:Enzyme Replacement Therapy; D006801:Humans; D050356:Lipid Metabolism; D008213:Lymphocyte Activation; D016464:Lysosomal Storage Diseases / Q000209:etiology* / Q000378:metabolism* / Q000628:therapy; D008247:Lysosomes / Q000378:metabolism; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism*; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D055610:Antigens, CD1d; C526877:CD1D protein, human
keywords: CD1d; Lysosomal storage diseases; NKT cells; lipids; lysosome