Obesity has reached epidemic proportions globally. At least 2.8 million people die each year as a result of being overweight or obese, the biggest burden being obesity-related diseases. It is now clear that inflammation, particularly in adipose tissue itself, interferes with insulin signaling and is an underlying cause or contributor to many of these diseases, including type 2 diabetes, atherosclerosis, and cancer. Recognition that the immune system can regulate metabolic pathways has prompted a new way of thinking about diabetes and weight management. Despite much recent progress, most immunometabolic pathways, and how to target them, are currently unknown. One such pathway is the cross-talk between invariant natural killer (iNKT) cells and neighboring adipocytes. iNKT cells are the innate lipid-sensing arm of the immune system. Since our discovery that mammalian adipose tissue is enriched for iNKT cells, we have identified a critical role for iNKT cells in regulating adipose inflammation and body weight. Adipose iNKT cells are unusual regulatory iNKT cells which we have shown, using parabiosis, are resident in adipose tissue. We study adipose iNKT cells to identify key signals and molecules used by iNKT cells to induce metabolic control and weight loss in obesity. We are also investigating potential lipid antigens in adipose tissue which may activate iNKT cells. This will perhaps explain iNKT cell conservation in adipose depots, and provide safe tools for iNKT cell manipulation in vivo.
Lynch, Immunology, Review 2014