Mast cells in the autonomic nervous system and potential role in disorders with dysautonomia and neuroinflammation

Theoharides, Theoharis C.; Twahir, Assma; Kempuraj, Duraisamy

doi:10.1016/j.anai.2023.10.032

Cited by 11 publications

(5 citation statements)

References 392 publications

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“…It is interesting that microglia communicate with [ 182 ], and can be activated by [ 183 ], mast cells, unique effector immune cells that are ubiquitous in the body and are critical in allergies [ 184 ], but also inflammatory processes [ 185 ]. Mast cells have also been implicated in the pathogenesis of neuroinflammatory diseases, such as multiple sclerosis, Long-COVID and autism spectrum disorder [ 16 ]. In fact, degranulated mast cells were reported to be increased, and were associated with myofibers and motor endplates in the quadriceps muscles of patients with ALS but not in controls [ 186 ].…”

Section: Amyotrophic Lateral Sclerosis (Als)mentioning

confidence: 99%

“…Chronic neuroinflammation can affect specific neuronal types in specific regions and induce specific neuroinflammatory and neurodegenerative disorders [ 12 ]. Mast cells release inflammatory molecules that can activate glia and induce neuroinflammation in neuroinflammatory disorders [ 15 , 16 ]. Microbial dysbiosis, leaky gut, and cerebral and vascular barriers are implicated in neurodegenerative disorders [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

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Recent Research Trends in Neuroinflammatory and Neurodegenerative Disorders

Cohen,

Mathew,

Dourvetakis

et al. 2024

Cells

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Neuroinflammatory and neurodegenerative disorders including Alzheimer’s disease (AD), Parkinson’s disease (PD), traumatic brain injury (TBI) and Amyotrophic lateral sclerosis (ALS) are chronic major health disorders. The exact mechanism of the neuroimmune dysfunctions of these disease pathogeneses is currently not clearly understood. These disorders show dysregulated neuroimmune and inflammatory responses, including activation of neurons, glial cells, and neurovascular unit damage associated with excessive release of proinflammatory cytokines, chemokines, neurotoxic mediators, and infiltration of peripheral immune cells into the brain, as well as entry of inflammatory mediators through damaged neurovascular endothelial cells, blood–brain barrier and tight junction proteins. Activation of glial cells and immune cells leads to the release of many inflammatory and neurotoxic molecules that cause neuroinflammation and neurodegeneration. Gulf War Illness (GWI) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are chronic disorders that are also associated with neuroimmune dysfunctions. Currently, there are no effective disease-modifying therapeutic options available for these diseases. Human induced pluripotent stem cell (iPSC)-derived neurons, astrocytes, microglia, endothelial cells and pericytes are currently used for many disease models for drug discovery. This review highlights certain recent trends in neuroinflammatory responses and iPSC-derived brain cell applications in neuroinflammatory disorders.

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Section: Amyotrophic Lateral Sclerosis (Als)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Recent Research Trends in Neuroinflammatory and Neurodegenerative Disorders

Cohen,

Mathew,

Dourvetakis

et al. 2024

Cells

Self Cite

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“…Mast cells, integral components of the immune system influenced by their microenvironment, accumulate at injury sites associated with various conditions, including wound healing, particularly near blood vessels ( 129 ). Mast cells are generally found throughout normal connective tissue, and they are usually next to blood vessels and peripheral nerves or beneath the epithelial layer ( 130 , 131 ). In the eye, they are predominantly found in the choroid of the eye but are absent in the neuroretina ( 132 ).. Studies have demonstrated an increased number and degranulation of mast cells in all forms of age-related macular degeneration, including nAMD ( 126 , 127 ).…”

Section: Potential Role Of Mast Cells In Cnv and Subretinal Fibrosismentioning

confidence: 99%

Exploring the role of granzyme B in subretinal fibrosis of age-related macular degeneration

Gill,

Yoo,

Chakravarthy

et al. 2024

Front. Immunol.

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Age-related macular degeneration (AMD), a prevalent and progressive degenerative disease of the macula, is the leading cause of blindness in elderly individuals in developed countries. The advanced stages include neovascular AMD (nAMD), characterized by choroidal neovascularization (CNV), leading to subretinal fibrosis and permanent vision loss. Despite the efficacy of anti-vascular endothelial growth factor (VEGF) therapy in stabilizing or improving vision in nAMD, the development of subretinal fibrosis following CNV remains a significant concern. In this review, we explore multifaceted aspects of subretinal fibrosis in nAMD, focusing on its clinical manifestations, risk factors, and underlying pathophysiology. We also outline the potential sources of myofibroblast precursors and inflammatory mechanisms underlying their recruitment and transdifferentiation. Special attention is given to the potential role of mast cells in CNV and subretinal fibrosis, with a focus on putative mast cell mediators, tryptase and granzyme B. We summarize our findings on the role of GzmB in CNV and speculate how GzmB may be involved in the pathological transition from CNV to subretinal fibrosis in nAMD. Finally, we discuss the advantages and drawbacks of animal models of subretinal fibrosis and pinpoint potential therapeutic targets for subretinal fibrosis.

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“…Neurological disorders present neuroinflammation mediated by MCs. For example, MCs were found in greater numbers in CNS lesions in patients suffering from MS and were found to produce higher levels of tryptase [ 4 ]. Experimental autoimmune encephalomyelitis (EAE) is an experimental model that mimics MS in some ways.…”

Section: Introductionmentioning

confidence: 99%

Impact of TNF and IL-33 Cytokines on Mast Cells in Neuroinflammation

Conti,

Ronconi,

Lauritano

et al. 2024

IJMS

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Mast cells (MCs) are derived from hematopoietic progenitors, mature in vascularized tissues, and participate in innate and acquired immunity. Neuroinflammation is a highly debated topic in the biomedical literature; however, the impact of tumor necrosis factor (TNF) and IL-33 on MCs in the brain has not been widely addressed. MCs can be activated by IgE binding to FcεRI, as well as by different antigens. After activation, MCs mediate various immunological and inflammatory responses through TNF and IL-33. TNF has two receptors: TNFR1, a p55 molecule, and TNFR2, a p75 molecule. This cytokine is the only one of its kind to be stored in the granules of MCs and can also be generated by de novo synthesis via mRNA. In the central nervous system (CNS), TNF is produced almost exclusively by microglial cells, neurons, astrocytes, and, minimally, by endothelial cells. After its release into brain tissue, TNF rapidly induces the adhesion molecules endothelial leukocyte adhesion molecule 1 (ELAM-1), intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) in endothelial cells. TNF causes the chemoattraction of neutrophils by inducing several molecules, including CXC chemokines (IL-8). Both MCs and microglial cells act as a primary barrier against foreign molecules in the CNS, producing pro-inflammatory cytokines such as IL-33. IL-33 belongs to the IL-1 family, is activated through the ST2L/IL1-RAcP receptor complex, and mediates both the innate and adaptive immune response. IL-33 is a nuclear transcription factor expressed in the brain, where it induces pro-inflammatory cytokines (TNF and IL-1) and chemokines (CCL2, CCL3, CCL5, and CXCL10). Therefore, MCs and microglia in the CNS are a source of pro-inflammatory cytokines, including TNF and IL-33, that mediate many brain diseases. The inhibition of TNF and IL-33 may represent a new therapeutic approach that could complement existing neuroinflammatory therapies.

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Mast cells in the autonomic nervous system and potential role in disorders with dysautonomia and neuroinflammation

Cited by 11 publications

References 392 publications

Recent Research Trends in Neuroinflammatory and Neurodegenerative Disorders

Recent Research Trends in Neuroinflammatory and Neurodegenerative Disorders

Exploring the role of granzyme B in subretinal fibrosis of age-related macular degeneration

Impact of TNF and IL-33 Cytokines on Mast Cells in Neuroinflammation

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