Lysosomal storage disorders prevent the proper action of some natural killer T (NKT) cells, according to Gadola et al. (page 2293).
NKT cells recognize glycosphingolipid (GSL) antigens presented on the surface of various cell types. Recognition of endogenous GSL antigens leads to the positive selection of NKT cells in the thymus. Once in the periphery, NKT cells can induce an immune response if presented with GSLs of foreign origin.
The overaccumulation of GSLs in lysosomes is a common feature of lysosomal storage disorders. Here, Gadola and colleagues show that this congestion impairs the intracellular processing and presentation of GSLs in the antigen-presenting cells of mouse models of lysosomal storage disorders.
The authors reasoned that, given their reliance on GSLs for selection, NKT cells might be impaired in the disease model mice. They found that, although the mice had normal NKT cells in terms of...
