The nervous and immune systems both serve as essential assessors and regulators of physiological function. Recently, there has been a great interest in how the nervous and immune systems interact to modulate both physiological and pathological states. In particular, the autonomic nervous system has a direct line of communication with immune cells anatomically, and moreover, immune cells possess receptors for autonomic neurotransmitters. This circumstantial evidence is suggestive of a functional interplay between the two systems, and extensive research over the past few decades has demonstrated neurotransmitters such as the catecholamines (i.e. dopamine, norepinephrine, and epinephrine) and acetylcholine have potent immunomodulating properties. Furthermore, immune cells, particularly T-lymphocytes, have now been found to express the cellular machinery for both the synthesis and degradation of neurotransmitters, which suggests the ability for both autocrine and paracrine signaling from these cells independent of the nervous system. The details underlying the functional interplay of this complex network of neuroimmune communication are still unclear, but this crosstalk is suggestive of significant implications on the pathogenesis of a number of autonomic-dysregulated and inflammation-mediated diseases. In particular, it is widely accepted that numerous forms of cardiovascular diseases possess imbalanced autonomic tone as well as altered T-lymphocyte function, but a paucity of literature exists discussing the direct role of neurotransmitters in shaping the inflammatory microenvironment during the progression or therapeutic management of these diseases. This review seeks to provide a fundamental framework for this autonomic neuroimmune interaction within T-lymphocytes, as well as the implications this may have in cardiovascular diseases.
Keywords: Acetylcholine; Anti-inflammatory reflex; Catecholamines; Hypertension; Neurotransmitters; T-lymphocytes.
Copyright © 2019 Elsevier Ltd. All rights reserved.
Conflict of interest statement
[Regulation of inflammatory responses by the autonomic nervous system].Nihon Rinsho Meneki Gakkai Kaishi. 2016;39(2):96-102. doi: 10.2177/jsci.39.96. Nihon Rinsho Meneki Gakkai Kaishi. 2016. PMID: 27212595 Review. Japanese.
Neuroimmune Modulation of Gut Function.Handb Exp Pharmacol. 2017;239:247-267. doi: 10.1007/164_2016_109. Handb Exp Pharmacol. 2017. PMID: 28035531 Review.
The Cholinergic and Adrenergic Autocrine Signaling Pathway Mediates Immunomodulation in Oyster Crassostrea gigas.Front Immunol. 2018 Feb 26;9:284. doi: 10.3389/fimmu.2018.00284. eCollection 2018. Front Immunol. 2018. PMID: 29535711 Free PMC article.
Catecholamines and acetylcholine are key regulators of the interaction between microbes and the immune system.Ann N Y Acad Sci. 2015 Sep;1351:39-51. doi: 10.1111/nyas.12792. Epub 2015 Jun 10. Ann N Y Acad Sci. 2015. PMID: 26378438 Review.
Catecholamines are synthesized by mouse lymphocytes and regulate function of these cells by induction of apoptosis.Immunology. 1996 May;88(1):140-6. doi: 10.1046/j.1365-2567.1996.d01-653.x. Immunology. 1996. PMID: 8707341 Free PMC article.