Neuro–epithelial–ILC2 crosstalk in barrier tissues

Group 2 innate lymphoid cells (ILC2s) contribute to the maintenance of mammalian barrier tissue homeostasis. We review how ILC2s integrate epithelial signals and neurogenic components to preserve the tissue microenvironment and modulate inflammation. The epithelium that overlies barrier tissues, including the skin, lungs, and gut, generates epithelial cytokines that elicit ILC2 activation. Sympathetic, parasympathetic, sensory, and enteric fibers release neural signals to modulate ILC2 functions. We also highlight recent findings suggesting neuro-epithelial-ILC2 crosstalk and its implications in immunity, inflammation and resolution, tissue repair, and restoring homeostasis. We further discuss the pathogenic effects of disturbed ILC2-centered neuro-epithelial-immune cell interactions and putative areas for therapeutic targeting.