Further Understanding of Neuro-Immune Interactions in Allergy: Implications in Pathophysiology and Role in Disease Progression

Abstract

The complicated interaction between the central and the autonomic (sympathetic, parasympathetic, and enteric) nervous systems on the one hand and the immune system and its components, on the other hand, seems to substantially contribute to allergy pathophysiology, uncovering an under-recognized association that could have diagnostic and therapeutic potentials. Neurons connect directly with and regulate the function of many immune cells, including mast cells, the cells that have a leading role in allergic disorders. Proinflammatory mediators such as cytokines, neurotrophins, chemokines, and neuropeptides are released by immune cells, which stimulate sensory neurons. The release of neurotransmitters and neuropeptides caused by the activation of these neurons directly impacts the functional activity of immune cells and vice versa, playing a decisive role in this communication. Successful application of Pavlovian conditioning in allergic disorders supports the existence of a psychoneuroimmunological interplay in classical allergic hypersensitivity reactions. Activation of neuronal homeostatic reflexes, like sneezing in allergic rhinitis, coughing in allergic asthma, and vomiting in food allergy, offers additional evidence of a neuroimmunological interaction that aims to maintain homeostasis. Dysregulation of this interaction may cause overstimulation of the immune system that will produce profound symptoms and exaggerated hemodynamic responses that will lead to severe allergic pathophysiological events, including anaphylaxis. In this article, we have systematically reviewed and discussed the evidence regarding the role of the neuro-immune interactions in common allergic clinical modalities like allergic rhinitis, chronic rhinosinusitis, allergic asthma, food allergy, atopic dermatitis, and urticaria. It is essential to understand unknown – to most of the immunology and allergy experts – neurological networks that not only physiologically cooperate with the immune system to regulate homeostasis but also pathogenetically interact with more or less known immunological pathways, contribute to what is known as neuroimmunological inflammation, and shift homeostasis to instability and disease clinical expression. This understanding will provide recognition of new allergic phenotypes/endotypes and directions to focus on specialized treatments, as the era of personalized patient-centered medicine, is hastening apace.

Profile of Urticaria and Angioedema Patients at Dr. Moewardi General Hospital Surakarta, Indonesia

“…Urticarial lesions may be accompanied by angioedema, which is asymmetric non-pitting edema of the lips, cheeks, legs, genital organs, and periorbital area. 19 Research by Kaplan in the United States (2017) reported that angioedema was only found in around 16% of patients with urticaria. 20 In this study, urticaria patients with angioedema were only found in 13.16% of patients (Table 2).…”

Endoscopic vidian and vidian‐branch neurectomy for refractory allergic rhinitis: A systematic review

“…3,11,54,55 In addition, the parasympathetic nervous system also participates in the dysregulation of neuro-immune interactions in the late phase, though the processes are not fully understood. 56,57 Therefore, either functionally or physically, inhibiting this reflex arc is expected to have a significant impact on the management of AR in clinical symptoms. The functional blocking of the reflex arc is currently treated pharmacologically with antihistamines and anticholinergic medications.…”

“…When engaged, these neurons cause glandular production and vasodilation, which cause rhinorrhea and nasal congestion 3,11,54,55 . In addition, the parasympathetic nervous system also participates in the dysregulation of neuro‐immune interactions in the late phase, though the processes are not fully understood 56,57 . Therefore, either functionally or physically, inhibiting this reflex arc is expected to have a significant impact on the management of AR in clinical symptoms.…”

Basophils in pruritic skin diseases

“…While IL-31RA is present on most basophils, OSMRβ can only be found on a small subpopulation ( 21 ). IL-31RA is expressed on half of dorsal root ganglia (DRG) with a size up to 30 µM ( 22 ), and its ligand can act as a neurotrophin on DRG neurons ( 94 ). Through activation of IL-31RA ( 22 ) on peripheral nerves, itch signals are transmitted to the central nervous system ( 21 ).…”