Neuronal IL-17 controlsC. elegansdevelopmental diapause through CEP-1/p53

Abstract How metazoan development is coordinated with nutrient availability remains unclear. Here, we show that the activity of CEP-1, the C. elegans ortholog of the tumor suppressor p53, switches organismal development between reproductive growth and dormancy by responding to nutrient availability signaled by neuronal cytokine, ILC-17.1. Specifically, ILC-17.1 is released from amphid neurons upon food availability and promotes glucose utilization and represses CEP-1/p53: CEP-1/p53 repression promotes growth. In the absence of ILC-17.1, CEP-1/p53 is activated, accumulates in post-embryonically dividing progenitor blast cells, upregulates cell-cycle inhibitors, decreases cytochrome C levels, and causes larvae to arrest as stress-resistant, quiescent dauers. We propose a model whereby ILC-17.1 signaling links nutrient availability and energy metabolism to cell cycle progression and cell fate decisions during development through CEP-1/p53. These findings also suggest that the developmental function of the p53-gene family could have shaped their evolution and are relevant to our understanding of neuroimmune mechanisms in cancer.