α-Galactosylceramide therapy for autoimmune diseases: prospects and obstacles

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Abstract
Autoimmune responses are normally kept in check by immune-tolerance mechanisms, which include regulatory T cells. In recent years, research has focused on the role of a subset of natural killer T (NKT) cells - invariant NKT (iNKT) cells, which are a population of glycolipid-reactive regulatory T cells - in controlling autoimmune responses. Because iNKT cells strongly react with a marine-sponge-derived glycolipid, alpha-galactosylceramide (alpha-GalCer), it has been possible to specifically target and track these cells. As I discuss here, although preclinical studies have shown considerable promise for the development of treatment with alpha-GalCer as a therapeutic modality for autoimmune diseases, several obstacles need to be overcome before moving alpha-GalCer therapy from the bench to the bedside.