Lipid accumulation in adipose tissue-resident iNKT cells contributes to an inflammatory phenotype

Reciprocal communication between adipocytes and immune cells is essential to maintain optimal adipose tissue (AT) functionality. Amongst others, adipocytes directly interact with invariant NKT cells (iNKT cells), which in turn secrete various cytokines. A lipid-rich microenvironment, as observed in obesity, skews this adipocyte-driven cytokine output towards a more inflammatory output. Whether a lipid-rich microenvironment also affects iNKT cells directly, however, is unknown. Here, we show that primary mouse iNKT cells isolated from AT can accumulate lipids in lipid droplets (LDs), more so than liver- and spleen-resident iNKT cells. Furthermore, a lipid-rich microenvironment increased the production of the proinflammatory cytokine IFNγ. Next, to an indirect, adipocyte-mediated cue, iNKT cells can directly respond to environmental lipid changes, supporting a potential role as nutrient sensors.