Natural killer T lymphocytes (NKT) have been implicated in the regulation of autoimmune processes in both mice and humans. In response to stimuli, this subset of cells rapidly produces large amounts of
cytokines thereby provoking immune responses, including protection against
autoimmune diseases. NKT cells are present in all lymphoid compartments, but are most abundant in the liver and bone marrow. They are activated by interaction of their
T-cell receptor with
glycolipids presented by CD1d, a nonpolymorphic, major histocompatibility complex class I-like molecule expressed by antigen presenting cells. Several possible
ligands for NKT cells have recently been suggested. beta-
glucosylceramide, a naturally occurring
glycolipid, is a metabolic intermediate in the anabolic and catabolic pathways of complex
glycosphingolipids. Like other beta-
glycolipids, beta-
glucosylceramide has an immunomodulatory effect in several immune mediated disorders, including immune mediated
colitis. Due to the broad impact that NKT cells have on the immune system, there is intense interest in understanding how NKT cells are stimulated and the extent to which NKT cell responses can be controlled. These novel
ligands are currently being evaluated in animal models of
colitis. Here, we discuss strategies to alter NKT lymphocyte function in various settings and the potential clinical applications of natural
glycolipids.