Mast Cells in the Pathogenesis of Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

Costanza, Massimo; Colombo, Mario P.; Pedotti, Rosetta

doi:10.3390/ijms131115107

Cited by 35 publications

(31 citation statements)

References 108 publications

(183 reference statements)

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“…IL-3 acts on various cell types, including mast cells, basophils, monocytes, DCs, B cells, T cells, and endothelial cells (14)(15)(16)(17)(18)(19)(20)(21). While the role of mast cells in EAE is somewhat controversial (44), other leukocyte subsets and transendothelial migration are clearly involved in development of encephalomyelitis (45)(46)(47)(48). According to our data, the main producers of IL-3 in EAE are CD4 + T cells.…”

Section: Discussionmentioning

confidence: 67%

IL-3 promotes the development of experimental autoimmune encephalitis

Renner¹,

Hellerbrand²,

Hermann³

et al. 2016

JCI Insight

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Little is known about the role of IL-3 in multiple sclerosis (MS) in humans and in experimental autoimmune encephalomyelitis (EAE). Using myelin oligodendrocyte glycoprotein (MOG) peptide-induced EAE, we show that CD4 T cells are the main source of IL-3 and that cerebral IL-3 expression correlates with the influx of T cells into the brain. Blockade of IL-3 with monoclonal antibodies, analysis of IL-3 deficient mice, and adoptive transfer of leukocytes demonstrate that IL-3 plays an important role for development of clinical symptoms of EAE, for migration of leukocytes into the brain, and for cerebral expression of adhesion molecules and chemokines. In contrast, injection of recombinant IL-3 exacerbates EAE symptoms and cerebral inflammation. In patients with relapsing-remitting MS (RRMS), IL-3 expression by T cells is markedly upregulated during episodes of relapse. Our data indicate that IL-3 plays an important role in EAE and may represent a new target for treatment of MS.

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Section: Discussionmentioning

confidence: 67%

IL-3 promotes the development of experimental autoimmune encephalitis

Renner¹,

Hellerbrand²,

Hermann³

et al. 2016

JCI Insight

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“…By nature of their immune regulatory role, mast cells participate in IgE switching by B cells [23] and the release of chemoattractants that recruit eosinophils [24] and monocytes. Disease states involving autoimmune demyelination are accompanied by an increased absolute number of mast cells within the CNS, as well as those undergoing degranulation [25], although controversial aspects of their function remain [26]. Upon degranulation, mast cells release algogenic substances which activate or sensitize nociceptors, thereby contributing directly to neuropathic pain [27].…”

Section: Glia and Mast Cells: The Dynamic Duo Of Neuroinflammationmentioning

confidence: 98%

N-Palmitoylethanolamine and Neuroinflammation: a Novel Therapeutic Strategy of Resolution

et al. 2015

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Inflammation is fundamentally a protective cellular response aimed at removing injurious stimuli and initiating the healing process. However, when prolonged, it can override the bounds of physiological control and becomes destructive. Inflammation is a key element in the pathobiology of chronic pain, neurodegenerative diseases, stroke, spinal cord injury, and neuropsychiatric disorders. Glia, key players in such nervous system disorders, are not only capable of expressing a pro-inflammatory phenotype but respond also to inflammatory signals released from cells of immune origin such as mast cells. Chronic inflammatory processes may be counteracted by a program of resolution that includes the production of lipid mediators endowed with the capacity to switch off inflammation. These naturally occurring lipid signaling molecules include the N-acylethanolamines, N-arachidonoylethanolamine (an endocannabinoid), and its congener N-palmitoylethanolamine (palmitoylethanolamide or PEA). PEA may play a role in maintaining cellular homeostasis when faced with external stressors provoking, for example, inflammation. PEA is efficacious in mast cell-mediated models of neurogenic inflammation and neuropathic pain and is neuroprotective in models of stroke, spinal cord injury, traumatic brain injury, and Parkinson disease. PEA in micronized/ultramicronized form shows superior oral efficacy in inflammatory pain models when compared to naïve PEA. Intriguingly, while PEA has no antioxidant effects per se, its co-ultramicronization with the flavonoid luteolin is more efficacious than either molecule alone. Inhibiting or modulating the enzymatic breakdown of PEA represents a complementary therapeutic approach to treat neuroinflammation. This review is intended to discuss the role of mast cells and glia in neuroinflammation and strategies to modulate their activation based on leveraging natural mechanisms with the capacity for self-defense against inflammation.

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“…These include mast cell tryptase in CSF from MS patients [ 60 ] and histamine levels in CSF from MS patients [ 61 , 62 ]. In spite of such evidence, the role of mast cells in MS is still somewhat controversial [ 63 ], in part because some mouse models of MS, such as induced EAE, have indicated that while mast cells can accumulate in EAE, they are “dispensable” [ 64 ]. Of course the limitation here is that it is an induced model of “MS” and in mice, which may not reflect the human condition very well.…”

Section: Multiple Sclerosismentioning

confidence: 99%

Curbing Inflammation in Multiple Sclerosis and Endometriosis: Should Mast Cells Be Targeted?

Hart

2015

International Journal of Inflammation

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Inflammatory diseases and conditions can arise due to responses to a variety of external and internal stimuli. They can occur acutely in response to some stimuli and then become chronic leading to tissue damage and loss of function. While a number of cell types can be involved, mast cells are often present and can be involved in the acute and chronic processes. Recent studies in porcine and rabbit models have supported the concept of a central role for mast cells in a “nerve-mast cell-myofibroblast axis” in some inflammatory processes leading to fibrogenic outcomes. The current review is focused on the potential of extending aspects of this paradigm into treatments for multiple sclerosis and endometriosis, diseases not usually thought of as having common features, but both are reported to have activation of mast cells involved in their respective disease processes. Based on the discussion, it is proposed that targeting mast cells in these diseases, particularly the early phases, may be a fruitful avenue to control the recurring inflammatory exacerbations of the conditions.

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Mast Cells in the Pathogenesis of Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

Cited by 35 publications

References 108 publications

IL-3 promotes the development of experimental autoimmune encephalitis

IL-3 promotes the development of experimental autoimmune encephalitis

N-Palmitoylethanolamine and Neuroinflammation: a Novel Therapeutic Strategy of Resolution

Curbing Inflammation in Multiple Sclerosis and Endometriosis: Should Mast Cells Be Targeted?

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