Neuro-immune regulation of mucosal physiology

Abstract

Mucosal barriers constitute major body surfaces that are in constant contact with the external environment. Mucosal sites are densely populated by a myriad of distinct neurons and immune cell types that sense, integrate and respond to multiple environmental cues. In the recent past, neuro-immune interactions have been reported to play central roles in mucosal health and disease, including chronic inflammatory conditions, allergy and infectious diseases. Discrete neuro-immune cell units act as building blocks of this bidirectional multi-tissue cross-talk, ensuring mucosal tissue health and integrity. Herein, we will focus on reciprocal neuro-immune interactions in the airways and intestine. Such neuro-immune cross-talk maximizes sensing and integration of environmental aggressions, which can be considered an important paradigm shift in our current views of mucosal physiology and immune regulation.

Blockade of RGMb inhibits allergen-induced airways disease

“…42 IL-25, in combination with neuropeptides, such as neuromedin U, which is released from sensory neurons in the lungs, and calcitonin gene-related peptide, which is released from pulmonary neuroendocrine cells, can promote type 2 immunity in allergen-driven AHR 1,2,43-45 by enhancing production of IL-4, IL-5, and IL-13 from ILC2s, T H 2 cells, and RGMb 1 interstitial macrophages. 2,23,[44][45][46] Although RGMb 1 interstitial macrophages in saline-treated control mice express only low levels of IL-17RB, we found that after either OVA or CRA sensitization and challenge, RGMb 1 interstitial macrophages were the most numerous IL-17RB-expressing cells, accounting for about 98% of IL-17RB 1 cells in the lung. Levels of both IL-25 and IL-17RB mRNA and protein increase in the lungs after infection with respiratory syncytial virus or rhinovirus 35,47 or after allergen exposure, as shown in the present study and in a previous study.…”

Neurite outgrowth in symptomatic uncomplicated diverticular disease

“…Based on these results, the authors speculate that interactions between macrophages and nerves could play a role in inducing symptoms in diverticular disease. In support of this hypothesis, several studies have now clearly showed that both in the central nervous system and in the GI tract, microglia and macrophages have the ability to promote axonal regeneration after damage but also in the context of chronic inflammatory conditions induce neuronal hyperexcitability leading to neuropathic pain …”

“…In support of this hypothesis, several studies have now clearly showed that both in the central nervous system and in the GI tract, microglia and macrophages have the ability to promote axonal regeneration after damage but also in the context of chronic inflammatory conditions induce neuronal hyperexcitability leading to neuropathic pain. 14,15 Interestingly, morphological and functional neuronal alterations in the gut wall have also been associated with functional disorders like IBS, sharing similar GI symptoms with diverticulosis. A previous study from Barbara and colleagues also demonstrated that patients with IBS showed a higher density of mucosal nerve fibers and active nerve sprouting compared with controls.…”

Future research trends in understanding the mechanisms underlying allergic diseases for improved patient care

“…55,56 Immune and neuronal cell types are found in large numbers at skin and mucosal barrier surfaces and are in close contact with each other forming a neuronal-immune cell network. [57][58][59][60] Both immune and neural cells detect and respond to environmental In addition to mediating allergic responses via immune responses, these proinflammatory mediators also directly activate sensory neurons that regulate itch, cough, sneezing, bronchoconstriction, and alterations in gastrointestinal motility. 59 On stimulation, sensory and autonomic neurons release neuropeptides and neurotransmitters such as substance P, neurokinin A, neuromedin U (NMU), calcitonin gene-related peptide, vasoactive intestinal peptide, acetylcholine, and norepinephrine that signal immune cells.…”