Innate lymphoid cells (ILCs) play an important role in the control and maintenance of barrier immunity. However, chronic activation of ILCs results in immune-mediated pathology. Here, we show that tissue-resident type 2 ILCs (ILC2s) display a distinct metabolic signature upon chronic activation. In the context of allergen-driven airway inflammation, ILC2s increase their uptake of both external lipids and glucose. Externally acquired fatty acids are transiently stored in lipid droplets and converted into phospholipids to promote the proliferation of ILC2s. This metabolic program is imprinted by interleukin-33 (IL-33) and regulated by the genes Pparg and Dgat1, which are both controlled by glucose availability and mTOR signaling. Restricting dietary glucose by feeding mice a ketogenic diet largely ablated ILC2-mediated airway inflammation by impairing fatty acid metabolism and the formation of lipid droplets. Together, these results reveal that pathogenic ILC2 responses require lipid metabolism and identify ketogenic diet as a potent intervention strategy to treat airway inflammation.

No abstract

Innate lymphoid cells (ILC) are a recently described group of tissue-resident immune cells that play essential roles in maintaining and protecting the tissue barrier against invading pathogens. Extensive research has revealed that ILC-mediated immune responses are controlled by dietary components and metabolites. An additional role of ILC as important direct regulators of host metabolism and glucose tolerance is emerging. This suggests that ILC may act as key dietary sensors integrating nutritional and metabolic stress to facilitate both maintenance of barrier sites and a coordinated immune response protecting these tissues. In this respect, investigations have begun to determine how different ILC responses are metabolically fueled and the impact of nutrient availability on the regulation of ILC function. Here, we discuss the current literature concerning dietary and metabolic control of ILC. In particular, we address whether the dietary and metabolic control of ILC and their simultaneous influence on host metabolism may function as a coordinated program of barrier defense.