Neuroimmune regulatory networks of the airway mucosa in allergic inflammatory disease

Abstract

Communication between the nervous and immune systems serves a key role in host‐protective immunity at mucosal barrier sites including the respiratory tract. In these tissues, neuroimmune interactions operate in bidirectional circuits that can sense and respond to mechanical, chemical, and biologic stimuli. Allergen‐ or helminth‐induced products can produce airway inflammation by direct action on nociceptive afferents and adjacent tissues. The activity of nociceptive afferents can regulate innate and adaptive immune responses via neuropeptides and neurotransmitter signaling. This review will summarize recent work investigating the role of neuropeptides CGRP, VIP, neuromedins, substance P, and neurotransmitters dopamine and the B2‐adrenoceptor agonists epinepherine/norepinepherine, each of which influence type 2 immunity by instructing mast cell, innate lymphoid cell type 2, dendritic cell, and T cell responses, both in the airway and the draining lymph node. Afferents in the airway also contain receptors for alarmins and cytokines, allowing their activity to be modulated by immune cell secreted products, particularly those secreted by mast cells. Taken together, we propose that further investigation of how immunoregulatory neuropeptides shape respiratory inflammation in experimental systems may reveal novel therapeutic targets for addressing the increasing prevalence of chronic airway disease in humans.

Neuromedins NMU and NMS: An Updated Overview of Their Functions

“…Therefore, these topics are not addressed in the present article. Interested readers are encouraged to refer to relevant papers on immunology and inflammation (122)(123)(124) and cancers (125).…”

Neuronal-Immune Cell Units in Allergic Inflammation in the Nose

“…However, research of neuro molecules in allergic rhinitis by proteomic and metabolomic techniques is still in progress. The nasal epithelium is richly innervated with olfactory, nociceptive sensory nerve fibers, as well as sympathetic and parasympathetic fibers [6]. The olfactory nerve fibers inside the cranial nerve I provide afferent innervation linked with the sensation of smell.…”

“…The endings of nociceptive sensory nerves inside a cranial nerve V' branch sense various stimuli: mechanical, chemical, hypertonic saline, cigarette smoke, thermal, aero-allergenic, etc. The sensory nerve ending secrete SP, NMU, VIP, and CGRP [6,104]. The parasympathetic system controls the nasal secretion and produces ACh, which controls mucus releasing, and VIP that stimulates the local vasodilatation.…”

“…The prevalence of allergic diseases, especially allergic rhinitis, is a challenge and provides a rationale for researchers' interest in this pathology. Single-cell RNA-sequencing (scRNA-seq) has enabled a revisal of the landscape of the nasal mucoliated barrier's cells in the nose in allergic rhinitis [6] and study has commenced of the neuroimmune cross-talk in the unified airway at the modern level [7][8][9][10][11]. Unfortunately, there are still many controversial research results of how single cells and neuro molecules interact in allergic inflammation.…”

“…However, the time has come when fundamental data of immunology and neuroscience are being introduced as novel diagnostic and therapeutic approaches into healthcare practice [6]. There are still inefficient medications used in allergic rhinitis, which should be re-studied in terms of the impact on neuronal-immune cell units because this may be a hidden cause behind the low efficacy of some drugs.…”