Neuro-immune crosstalk and allergic inflammation

Abstract

The central nervous system (CNS) and peripheral tissues are connected by the peripheral nervous system (PNS), which transmitsThe neuronal and immune systems exhibit bidirectional interactions that play a critical role in tissue homeostasis, infection, and inflammation. Neuron-derived neuropeptides and neurotransmitters regulate immune cell functions, whereas inflammatory mediators produced by immune cells enhance neuronal activation. In recent years, accumulating evidence suggests that peripheral neurons and immune cells are colocalized and affect each other in local tissues. A variety of cytokines, inflammatory mediators, neuropeptides, and neurotransmitters appear to facilitate this crosstalk and positivefeedback loops between multiple types of immune cells and the central, peripheral, sympathetic, parasympathetic, and enteric nervous systems. In this Review, we discuss these recent findings regarding neuro-immune crosstalk that are uncovering molecular mechanisms that regulate inflammation. Finally, neuro-immune crosstalk has a key role in the pathophysiology of allergic diseases, and we present evidence indicating that neuro-immune interactions regulate asthma pathophysiology through both direct and indirect mechanisms.

Neuro-Immune Circuits Regulate Immune Responses in Tissues and Organ Homeostasis

“…respective neuronal subsets is therefore based on the expression of enzymes involved in neurotransmitter synthesis such as tyrosine hydroxylase for sympathetic catecholaminergic neurons and choline acetyltransferase (Chat) for parasympathetic cholinergic neurons (17). Because many different immune cells express the receptor for norepinephrine, such as α-and β-adrenoreceptors, the sympathetic nervous system is tightly linked to immune regulation (18). Potentially as a part of the fight-and-flight reaction that need to ensure survival of the organism, the sympathetic nervous system initially has a pro-inflammatory function (19).…”

“…Thus, further experiments need to clarify the exact interaction between sensory neurons and epithelial cells. Sensory neurons respond to a broad variety of chemical and physical stimuli that can activate different ion channels, such as transient receptor potential vanilloid (TRPV1), transient receptor potential ankyrin 1 (TRPA1) and transient receptor potential cation channel subfamily M member 8 (TRPM8) (18,47). An important class of sensory neurons are nociceptors that are able to detect noxious stimuli such as heat, chemical and mechanical perturbations (48).…”

“…Mast cells have also been implicated in atopic dermatitis, where dermal lesions are hyper-innervated with a high abundance of substance P fibers and an increased respective receptor expression on mast cells (111). Nerve-derived substance P induced the rapid release of histamine, TNF, leukotriene B4, and vascular endothelial growth factor by mast cells suggesting a close interaction of neurons and mast cells in allergic diseases (18,112,113). This neuronal-mast cell connection has been underlined in the context of allergic skin disease models in mice.…”

Neuroimmunogastroenterology: At the Interface of Neuroimmunology and Gastroenterology

“…Catecholamines, a major class of sympathetic neurotransmitters, have been shown to differentially induce pro-(M1-like) and anti-(M2-like) inflammatory macrophages in the intestine (15). The effect of catecholamine signaling appears to be context-dependent as activation of α2 adrenoreceptors promotes the production of proinflammatory cytokines (16,17) whereas activation of β2 adrenoreceptors promotes the production of anti-inflammatory cytokines (18). Mast cells express adrenergic receptors, and signaling through these receptors can modulate the secretion of mast cell products (19).…”

“…Mast cells express adrenergic receptors, and signaling through these receptors can modulate the secretion of mast cell products (19). In contrast, the major parasympathetic neurotransmitter, acetylcholine, has been shown to decrease pro-inflammatory cytokine production in macrophages and dendritic cells, among other immune cell types (18,20,21). Serotonin, 95% of which is synthesized in the gut (22), modulates the polarization of macrophages (23) and phagocytosis (24).…”