Eosinophils are dispensable for development of MOG35–55-induced experimental autoimmune encephalomyelitis in mice

Ruppova, Klara; Lim, Jin Ho; Fodelianaki, Georgia; August, Avery; Neuwirth, Aleš

doi:10.1016/j.imlet.2021.09.001

Cited by 3 publications

(3 citation statements)

References 16 publications

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“…Elevated CCL11 was detected in the CSF and lymph nodes (but not in the serum) and correlated with decreased ED1 + /Iba1 + macrophages in the spinal cord and with protecting the integrity of the blood-brain barrier (99). In contrast, CCL11 was found to be elevated in the spinal cords of mice undergoing MOG 35−55 EAE (100). As CCL11 has been implicated in systemic inflammation and as a pathogenic factor in a range of neurodegenerative and neuroinflammatory diseases [reviewed in (101)], reduced CCL11 in the serum by the KD is consistent with an anti-inflammatory milieu.…”

Section: Discussionmentioning

confidence: 93%

Dietary protection against the visual and motor deficits induced by experimental autoimmune encephalomyelitis

Zyla-Jackson

Walton²,

Plafker³

et al. 2023

Front. Neurol.

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IntroductionFive to eight percent of the world population currently suffers from at least one autoimmune disorder. Despite multiple immune modulatory therapies for autoimmune demyelinating diseases of the central nervous system, these treatments can be limiting for subsets of patients due to adverse effects and expense. To circumvent these barriers, we investigated a nutritional intervention in mice undergoing experimental autoimmune encephalomyelitis (EAE), a model of autoimmune-mediated demyelination that induces visual and motor pathologies similar to those experienced by people with multiple sclerosis (MS).MethodsEAE was induced in female and male mice and the impact of limiting dietary carbohydrates by feeding a ketogenic diet (KD) enriched in medium chain triglycerides (MCTs), alpha-linolenic acid (an omega-3 fatty acid), and fiber was evaluated in both a preventive regimen (prior to immunization with MOG antigen) and an interventional regimen (following the onset of symptoms). Motor scores were assigned daily and visual acuity was measured using optokinetic tracking. Immunohistochemical analyses of optic nerves were done to assess inflammatory infiltrates and myelination status. Fatty acid and cytokine profiling from blood were performed to evaluate systemic inflammatory status.ResultsThe KD was efficacious when fed as a preventive regimen as well as when initiated as an interventional regimen following symptom onset. The KD minimally impacted body weight during the experimental time course, increased circulating ketones, prevented motor and ocular deficits, preserved myelination of the optic nerve, and reduced infiltration of immune cells to optic nerves. The KD also increased anti-inflammatory-associated omega-3 fatty acids in the plasma and reduced select cytokines in the circulation associated with EAE-mediated pathological inflammation.DiscussionIn light of ongoing clinical trials using dietary strategies to treat people with MS, these findings support that a KD enriched in MCTs, omega-3 fatty acids, and fiber promotes a systemic anti-inflammatory milieu and ameliorates autoimmune-induced demyelinating visual and motor deficits.

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Section: Discussionmentioning

confidence: 93%

Dietary protection against the visual and motor deficits induced by experimental autoimmune encephalomyelitis

Zyla-Jackson

Walton²,

Plafker³

et al. 2023

Front. Neurol.

View full text Add to dashboard Cite

show abstract

“…Elevated CCL11 was detected in the CSF and lymph nodes (but not in the serum) and correlated with decreased ED1 + /Iba1 + macrophages in the spinal cord and with protecting the integrity of the blood-brain barrier (99). In contrast, CCL11 was found to be elevated in the spinal cords of mice undergoing MOG 35-55 EAE (100). As CCL11 has been implicated in systemic inflammation and as a pathogenic factor in a range of neurodegenerative and neuroinflammatory diseases (reviewed in (101)), reduced CCL11 in the serum by the KD is consistent with an anti-inflammatory milieu.…”

Section: Discussionmentioning

confidence: 99%

Dietary Protection Against the Visual and Motor Deficits Induced by Experimental Autoimmune Encephalomyelitis

Zyla-Jackson

Walton

Plafker

et al. 2022

Preprint

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5-8% of the world population currently suffers from at least one autoimmune disorder. Despite multiple immune modulatory therapies for autoimmune demyelinating diseases of the CNS, these treatments are restricted to subsets of patients. To overcome these barriers, we investigated a nutritional intervention in mice undergoing experimental autoimmune encephalomyelitis (EAE). This model of autoimmune-mediated demyelination induces visual and motor pathologies similar to those experienced by patients with multiple sclerosis. Here, we report that limiting dietary carbohydrates by feeding mice a well-formulated ketogenic diet (WFKD) enriched in medium chain triglycerides, alpha-linolenic acid, and fiber protects from EAE-induced optic neuritis and motor deficits. The WFKD increased circulating ketones but did not cause weight gain while preserving visual acuity and motor function in both female and male EAE mice. Immunohistochemistry of optic nerves revealed that the WFKD preserved oligodendrocytes and reduced infiltrating T cells and macrophages. The WFKD also increased anti-inflammatory-associated omega-3 fatty acids in the plasma and reduced select cytokines in the circulation associated with inflammation and EAE pathologies. In support of ongoing clinical trials using dietary strategies to treat MS patients, these findings support that a WFKD promotes a systemic anti-inflammatory milieu that mitigates autoimmune-induced demyelinating visual and motor deficits.

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“…They share phenotypic and functional characteristics with MCs, which have significant protective benefits after spinal cord damage and traumatic brain injury [ 301 ], despite being one of the most pro-inflammatory cell types in the body. To date, little is known of the potential significance of basophils or eosinophils in MS. An increased number of basophils have been reported in MS compared to healthy individuals [ 302 ], and while eosinophil numbers and EOTAXIN-1 concentration were notably higher following MOG 35–55 -induced EAE in C57BL/6 mice when ablated in a mouse model, there was no effect on neuroinflammation, demyelination nor clinical progression, indicating that they were not required for disease progression [ 302 , 303 ].…”

Section: Eosinophils and Basophilsmentioning

confidence: 99%

The Plasticity of Immune Cell Response Complicates Dissecting the Underlying Pathology of Multiple Sclerosis

Sarkar,

Willson,

Jordan

2024

Journal of Immunology Research

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Multiple sclerosis (MS) is a neurodegenerative autoimmune disease characterized by the destruction of the myelin sheath of the neuronal axon in the central nervous system. Many risk factors, including environmental, epigenetic, genetic, and lifestyle factors, are responsible for the development of MS. It has long been thought that only adaptive immune cells, especially autoreactive T cells, are responsible for the pathophysiology; however, recent evidence has indicated that innate immune cells are also highly involved in disease initiation and progression. Here, we compile the available data regarding the role immune cells play in MS, drawn from both human and animal research. While T and B lymphocytes, chiefly enhance MS pathology, regulatory T cells (Tregs) may serve a more protective role, as can B cells, depending on context and location. Cells chiefly involved in innate immunity, including macrophages, microglia, astrocytes, dendritic cells, natural killer (NK) cells, eosinophils, and mast cells, play varied roles. In addition, there is evidence regarding the involvement of innate-like immune cells, such as γδ T cells, NKT cells, MAIT cells, and innate-like B cells as crucial contributors to MS pathophysiology. It is unclear which of these cell subsets are involved in the onset or progression of disease or in protective mechanisms due to their plastic nature, which can change their properties and functions depending on microenvironmental exposure and the response of neural networks in damage control. This highlights the need for a multipronged approach, combining stringently designed clinical data with carefully controlled in vitro and in vivo research findings, to identify the underlying mechanisms so that more effective therapeutics can be developed.

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Eosinophils are dispensable for development of MOG35–55-induced experimental autoimmune encephalomyelitis in mice

Cited by 3 publications

References 16 publications

Dietary protection against the visual and motor deficits induced by experimental autoimmune encephalomyelitis

Dietary protection against the visual and motor deficits induced by experimental autoimmune encephalomyelitis

Dietary Protection Against the Visual and Motor Deficits Induced by Experimental Autoimmune Encephalomyelitis

The Plasticity of Immune Cell Response Complicates Dissecting the Underlying Pathology of Multiple Sclerosis

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