Interaction of neurotransmitters and neurochemicals with lymphocytes

Kerage, Daniel; Sloan, Erica K.; Mattarollo, Stephen R.; McCombe, Pamela A.

doi:10.1016/j.jneuroim.2019.04.006

Cited by 63 publications

(57 citation statements)

References 328 publications

(388 reference statements)

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“…For example, failure of intact SNS signaling impairs the steady-state circadian rhythmicity of hematopoietic stem cells and disturbs their mobilization [123]. Basic βadrenoreceptor (β-AR) activity is programmed to retain lymphocytes within the lymph nodes, while activation of β-AR results in a rapid decline in lymphocytes in peripheral blood and lymphatic fluid by blocking efficient emigration [96,124]. Further studies provided evidence that activation of β-AR in T cells promotes interactions between β-AR and C-C motif chemokine receptor (CCR)7 and CCR4 [96].…”

Section: Sympathetic Nervous Systemmentioning

confidence: 99%

Sepsis-associated encephalopathy: a vicious cycle of immunosuppression

Ren

Yao

Zhang

et al. 2020

J Neuroinflammation

177

131

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Sepsis-associated encephalopathy (SAE) is commonly complicated by septic conditions, and is responsible for increased mortality and poor outcomes in septic patients. Uncontrolled neuroinflammation and ischemic injury are major contributors to brain dysfunction, which arises from intractable immune malfunction and the collapse of neuroendocrine immune networks, such as the cholinergic anti-inflammatory pathway, hypothalamic-pituitaryadrenal axis, and sympathetic nervous system. Dysfunction in these neuromodulatory mechanisms compromised by SAE jeopardizes systemic immune responses, including those of neutrophils, macrophages/monocytes, dendritic cells, and T lymphocytes, which ultimately results in a vicious cycle between brain injury and a progressively aberrant immune response. Deep insight into the crosstalk between SAE and peripheral immunity is of great importance in extending the knowledge of the pathogenesis and development of sepsis-induced immunosuppression, as well as in exploring its effective remedies.

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Section: Sympathetic Nervous Systemmentioning

confidence: 99%

Sepsis-associated encephalopathy: a vicious cycle of immunosuppression

Ren

Yao

Zhang

et al. 2020

J Neuroinflammation

177

131

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“…In our previous study, we have seen the expression of muscarinic acetylcholine receptor (subtype M2) on lymphocytes and DCs in mouse Peyers' patches 33 . Some other studies also showed that neurotransmitters such as acetylcholine and dopamine regulated the functions of B/T cells and DC/macrophages 34,35 . Some neurotransmitters are immunosuppressive, while others may stimulate and activate immunity 35,36 .…”

Section: Discussionmentioning

confidence: 97%

“…Some other studies also showed that neurotransmitters such as acetylcholine and dopamine regulated the functions of B/T cells and DC/macrophages 34,35 . Some neurotransmitters are immunosuppressive, while others may stimulate and activate immunity 35,36 . Thirdly, inflammatory mediators such as pro-inflammatory cytokines, prostaglandins, serotonin, and histamine from immune cells (even from neural cells or glial cells) can have variable effects on nerves of PNS 37,38 .…”

Section: Discussionmentioning

confidence: 97%

Distribution of nerve fibers and nerve-immune cell association in mouse spleen revealed by immunofluorescent staining

Al-Shalan

Shi

et al. 2020

Sci Rep

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The central nervous system regulates the immune system through the secretion of hormones from the pituitary gland and other endocrine organs, while the peripheral nervous system (PNS) communicates with the immune system through local nerve-immune cell interactions, including sympathetic/parasympathetic (efferent) and sensory (afferent) innervation to lymphoid tissue/organs. However, the precise mechanisms of this bi-directional crosstalk of the PNS and immune system remain mysterious. To study this kind of bi-directional crosstalk, we performed immunofluorescent staining of neurofilament and confocal microscopy to reveal the distribution of nerve fibers and nerveimmune cell associations inside mouse spleen. Our study demonstrates (i) extensive nerve fibers in all splenic compartments including the splenic nodules, periarteriolar lymphoid sheath, marginal zones, trabeculae, and red pulp; (ii) close associations of nerve fibers with blood vessels (including central arteries, marginal sinuses, penicillar arterioles, and splenic sinuses); (iii) close associations of nerve fibers with various subsets of dendritic cells, macrophages (Mac1 + and F4/80 +), and lymphocytes (B cells, T helper cells, and cytotoxic T cells). Our data concerning the extensive splenic innervation and nerve-immune cell communication will enrich our knowledge of the mechanisms through which the PNS affects the cellular-and humoral-mediated immune responses in healthy and infectious/noninfectious states. The human nervous system includes the central nervous system (CNS; containing the brain and spinal cord) and the peripheral nervous system (PNS; containing the sensory (somatic sensory and visceral sensory) and motor (somatic motor divisions and the autonomic nervous system (ANS; including sympathetic, parasympathetic, and enteric components))) 1. Recent studies have demonstrated that bi-directional communication/interaction between the nervous system and the immune system plays a crucial role in the host's responses to pathogen invasion, tissue injury, and other homeostatic dangers/threats 1-5. The functional organization of the neural control of the immune system is based on principles of reflex regulation 6. For example, the immune system is regulated by the CNS through the secretion of hormones from the pituitary and other neuroendocrine/endocrine organs 7,8 and by the PNS through local nerve (fiber)-immune cell interactions. The PNS can regulate the development, deployment, and homeostatic regulation of the immune system 3. This type of local neuroimmune interaction involves the "hardwiring" of sympathetic/parasympathetic (efferent) and visceral sensory (afferent) nerves to primary and secondary lymphoid tissue/organs 4-6. Neurotransmitters (e.g., acetylcholine, norepinephrine, and histamine) and neuropeptides (e.g., vasoactive intestinal peptide and substance P) released from nerve terminals (or even from the immune cells) might modulate the immune response in homeostasis and diseases 9. Cytokines and other immunologic factors synthesized a...

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“…Indeed, neurons and immune cells share a broad collection of surface receptors, secretory molecules, and signal transducers 82 . In particular, many neurotransmitters/neuropeptides and their synthesis/degradation machineries traditionally considered speci c for neurons are expressed in immune cells, although their functions in the immune system are to a large extent still unknown 83,84 . Studying these molecules and their regulatory mechanisms may provide new perspectives in tumour immunology and identifying new drug targets for cancer immunotherapies, as exempli ed by our current nding of this "MAO-A-ROS axis" regulation of TAM polarization in the TME.…”

Section: Discussionmentioning

confidence: 99%

Targeting monoamine oxidase A-regulated TAM polarization for cancer immunotherapy

Wang

et al. 2020

Preprint

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Abstract Targeting tumour-associated macrophages (TAMs) is a promising strategy to modify the immunosuppressive tumour microenvironment and improve cancer immunotherapy. Monoamine oxidase A (MAO-A) is an enzyme best known for its function in the brain; small molecule MAO inhibitors (MAOIs) are clinically used for treating neurological disorders. Here we observed MAO-A induction in mouse and human TAMs. MAO-A-deficient mice exhibited decreased TAM immunosuppressive functions corresponding with enhanced antitumour immunity. MAOI treatment induced TAM reprogramming and suppressed tumour growth in preclinical mouse syngeneic and human xenograft tumour models. Combining MAOI and anti-PD-1 treatments resulted in synergistic tumour suppression. Clinical data correlation studies associated high intratumoural MAOA expression with poor patient survival in a broad range of cancers. We further demonstrated that MAO-A promotes TAM immunosuppressive polarization via upregulating oxidative stress. Together, these data identify MAO-A as a critical regulator of TAMs and support repurposing MAOIs for TAM reprogramming to improve cancer immunotherapy.

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Interaction of neurotransmitters and neurochemicals with lymphocytes

Cited by 63 publications

References 328 publications

Sepsis-associated encephalopathy: a vicious cycle of immunosuppression

Sepsis-associated encephalopathy: a vicious cycle of immunosuppression

Distribution of nerve fibers and nerve-immune cell association in mouse spleen revealed by immunofluorescent staining

Targeting monoamine oxidase A-regulated TAM polarization for cancer immunotherapy

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