Influence of pulmonary neuroendocrine cells on lung homeostasis

Abstract

Pulmonary neuroendocrine cells (PNECs) – a unique cell population identified at all levels in the epithelium of the respiratory tract, histophysiology of which is still poorly understood. Given its important role as one of the main regulators of the respiration processes and homeostasis, its studying is one of the urgent tasks of medicine.According to the International Terms for Human Cytology and Histology published by the Federative International Committee on Anatomical Terminology (FICAT) under the writing of Wolters Kluwer and Lippincott Williams & Wilkins (2008), these cells are called respiratory neuroendocrine cells (in the trachea) or respiratory endocrine cells (in the bronchial tree). However, these cells have documented in modern international scientific literature as pulmonary neuroendocrine cells.The aim of this work is to analyze the modern scientific literature data on the effect of PNECs on the lung homeostasis in normal and pathological conditions.PNECs and their clusters – neuroepithelial bodies act as factors that regulate lung growth and maturation in embryogenesis via secretion of serotonin and gastrin-releasing hormone. In postnatal ontogenesis, PNEC secretion products – amines and neuropeptides, are characterized by participation in various physiological and pathological processes in the lung. PNECs normally maintain neurohumoral control over vascular and airway smooth muscle tone, act as peripheral chemoreceptors, and also are responsible for regulation of cell proliferation, differentiation, and mucus production from the respiratory epithelium. In case of respiratory tract damage, PNECs are capable of transdifferentiation by activating the Notch signaling pathway and renewal of other cellular types of respiratory epithelium. PNECs have a neuroimmunomodulating effect by means of neuropeptides and neurotransmitters secretion, which maintain and enhance the airways inflammatory response to an allergen. After the allergen exposition, PNECs activate type 2 innate lymphoid cells (ILC2) which being modulated by the neuropeptide CGRP produce type 2 cytokines IL-5 and IL-13, thereby contributing to an allergic response in the airways. At the same time, secreted by the PNECs neurotransmitter γ-aminobutyric acid (GABA) interacts with IL-13 to activate goblet cell mucus secretion. ILC2 induce eosinophilic inflammation and airways hypersensitivity. Recent studies have shown that ILC2 cells also stimulate Th2-associated immune response. Thus, CGRP and GABA are the key products of PNEC, which stimulate the Th2-associated immune response in the lung.Conclusions. Pulmonary neuroendocrine cells together with immune cells form a neuroimmunological module for the reception and response to environmental chemoattractants. The data on the role of pulmonary neuroendocrine cells in the airways allergic inflammation are still controversial in the literature, which necessitates further study of this issue.