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.
Highlights
The lysosome, designated as the recycling compartment of the cell, was initially described by Christian de Duve in 1955 [1]
GSLs were shown to be antigenic for Natural Killer T (NKT) cells, a group of lipid-specific T lymphocytes with important functions in autoimmunity, infection, and cancer [5]
This review focuses on CD1d-restricted T cells, the NKT cells, the most studied lipid-specific T cells [6]
Summary
The lysosome, designated as the recycling compartment of the cell, was initially described by Christian de Duve in 1955 [1]. It is a membrane-enclosed organelle, characterized by its acidic pH and the presence of a large number of hydrolases. The main feature of LSDs is the accumulation of different types of molecules in the lysosome, leading to a disturbance in lysosomal homeostasis that has important implications in autophagy, protein degradation, and metabolic stress [2,3]. The most common LSDs are sphingolipidoses, which are usually characterized by the accumulation of glycosphingolipids (GSLs): ceramide or sphingosine molecules modified by the addition of sugar head groups. GSLs were shown to be antigenic for Natural Killer T (NKT) cells, a group of lipid-specific T lymphocytes with important functions in autoimmunity, infection, and cancer [5]
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