Sensing of physiological regulators by innate lymphoid cells

摘要

ILC functions are regulated through extensive integration of dietary-derived metabolites and neuroendocrine signals. Enteric neurons that produce VIP and NMU stimulate ILC2 IL-5 and IL-13 secretion, leading to eosinophil recruitment and mucus production by goblet cells. Norepinephrine secreted by the sympathetic nervous system inhibits ILC2 function. DHT inhibits ILC2 proliferation and cytokine production. Glial cell GFL secretion induces ILC3 IL-22 production. Dietary-derived metabolites influence ILC functions. These include vitamins A and D, AHR ligands, prostaglandins and leukotrienes. While prostaglandins negatively regulate ILC2 functions, these lipid-derived molecules induce ILC3 IL-22 secretion. In contrast, leukotrienes impede ILC2 cytokine release. Vitamins have opposite effects on ILC2s and ILC3s. While RA inhibits ILC2 activity, it promotes ILC3 IL-22 production. Vitamin D is a negative regulator of ILC3 functions. Finally, AHR ligands are potent inducers of ILC3 IL-22 secretion. The green and red arrows indicate positive and negative regulators of ILC functions, respectively. ILC innate lymphoid cell, IL interleukin, VIP vasoactive intestinal peptide, NMU neuromedin U, GFL glial-derived neurotrophic factor family of ligands, RA retinoic acid (vitamin A), VitD3 vitamin D3, PG prostaglandin, LT leukotriene, AHR aryl hydrocarbon receptor, DHT dihydrotestosterone