RT Journal Article SR Electronic T1 Neuronal IL-17 controls C. elegans developmental diapause through p53/CEP-1 JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.11.22.517560 DO 10.1101/2022.11.22.517560 A1 Abhishiktha Godthi A1 Srijit Das A1 Johnny Cruz-Corchado A1 Andrew Deonarine A1 Kara Misel-Wuchter A1 Priya D. Issuree A1 Veena Prahlad YR 2022 UL http://biorxiv.org/content/early/2022/11/24/2022.11.22.517560.abstract AB Metazoan growth and development requires the coordination of cell cycle progression and metabolism with nutrient availability1–3. Here, we show that in C. elegans, amphid neurons regulate the animals’ developmental decision to continue reproductive growth or arrest as quiescent dauer larvae in response to food, by controlling the activity of C. elegans p53-like ortholog, CEP-1. Specifically, upon food availability, larval neurons secrete a mammalian IL-17 ortholog, ILC-17.1, and ILC-17.1 signaling is needed for C. elegans to progress through development into reproductive adults. ILC-17.1 deficiency activates CEP-1/p53 in larval blast cells, and causes larvae to arrest as stress-resistant, quiescent dauers by activating DAF-16/FOXO, decreasing cytochrome C levels, decreasing glucose utilization, and upregulating cell cycle inhibitors. Increasing ILC-17.1 levels represses CEP-1/p53 and promotes anabolic growth, but also inhibits apoptosis upon genotoxic stress. IL-17 also represses p53 in human epithelial cells. These studies describe a role for the tumor suppressor p53-like proteins in controlling developmental quiescence of a metazoan in response to neuronal activity and immunometabolic signals and are relevant to our understanding of neuroimmune mechanisms in cancer. This novel role for p53-like proteins in C. elegans supports the argument that their developmental function was a main driving force in their evolution4,5.Competing Interest StatementThe authors have declared no competing interest.