Innate lymphoid cells-key immune integrators of overall body homeostasis

The maintenance of the tissue barrier is essential to protect the host from external pathogens, thus ensuring the survival of the organism. This process requires the integration of various physiological signals originating from the digestive, immune, endocrine, and the nervous system as indicators of overall body fitness. Innate lymphoid cells (ILC) are a group of immune cells equipped for the guarding and maintenance of the tissue barrier against invading pathogens. Extensive research has focused on the regulation of ILC by cytokines derived from immune or non-immune cells, such as the epithelium. However, recent findings suggest that ILC may play an additional role in the monitoring of the overall health status of the host. This requires the combined sensing of cytokines, metabolites, hormones, and neuropeptides. ILC appear to be essential in this process functioning as hubs for the integration of different physiological signals to facilitate barrier immunity. Here, we discuss the emerging literature revealing dietary, metabolic, hormonal, and neuronal signals as important controllers and modulators of ILC function in health and disease.