Their findings, published in Nature Communications, reveal how dendritic cells adapt to the large lipid burden generated by engulfing dying cells and prevent that burden from disrupting immune balance. The researchers found that in dendritic cells, IRE1 can also be activated after the cells engulf dying cells and acquire a substantial cholesterol load. “Rather than responding only to classical cellular stress, IRE1 acts as a sensor that helps these immune cells adapt to the metabolic consequences of processing dying cells.” In mice lacking IRE1 specifically in dendritic cells, the immune system was less efficient at activating T cells in response to material derived from dying cells. Nevertheless, identifying IRE1 as a regulator of cholesterol homeostasis in dendritic cells could open new avenues for studying how immune cells respond to chronic lipid stress.