Figure 2.

ILC2 in the in lungs. ILC2 activity is rapidly induced by the first breath which promotes IL-33 secretion in the lungs. IL-33 acts on ILC2s to induce their production of both IL-5 and IL-13 that regulate the homeostasis of eosinophils and M2 macrophages. IL-33 also promotes ILC2 activity through the secretion of calcitonin gene‐related peptide (CGRP) produced by pulmonary neuroendocrine cells (PNECs). IL-5 derived from ILC2s, which are stimulated by VIP, further promotes vasoactive intestinal peptide (VIP) production by pulmonary c-fibers, creating a positive feedback loop. The parasympathetic nervous system (PNS) and SNS mainly act as negative feedback loop in response to inflammatory signals and prevent tissue damage.