The action of TH17 cells on blood brain barrier in multiple sclerosis and experimental autoimmune encephalomyelitis

Bălaşa, Rodica; Bărcuțean, Laura; Bălaşa, A; Moţăţăianu, Anca; Roman-Filip, Corina; Manu, Doina

doi:10.1016/j.humimm.2020.02.009

Cited by 66 publications

(46 citation statements)

References 58 publications

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“…EAE in mice is a commonly used animal model of human inflammatory demyelinating diseases, and involves a combination of immunopathological and neuropathological mechanisms that result in the development of clinical features that approximates the key pathological features of MS which include neuroinflammation, demyelination, axonal loss, and gliosis 9‐12 . The formation and accumulation of EAE or MS lesions is traditionally thought of as a consequence of the disruption of the blood‐brain barrier allowing the passage of pro‐inflammatory T‐cells into the brain where they become sensitized to proteins specific to mature myelinating oligodendrocytes within the CNS thereby resulting in loss of oligodendrocytes, and axonal demyelination and neurodegeneration 32 . The blood‐brain barrier is formed by the brain endothelial cells coated with basement membrane together with pericytes and astrocyte end‐feet facing parenchyma 33 .…”

Section: Discussionmentioning

confidence: 99%

“…B and C, Immunofluorescence staining for FABP5 (green) in the cell bodies of neurons co-stained with neuronspecific anti-NeuN antibodies (red) in the brain tissue of (B) non-MS and (C) MS tissue donors MS lesions is traditionally thought of as a consequence of the disruption of the blood-brain barrier allowing the passage of pro-inflammatory T-cells into the brain where they become sensitized to proteins specific to mature myelinating oligodendrocytes within the CNS thereby resulting in loss of oligodendrocytes, and axonal demyelination and neurodegeneration. 32 The blood-brain barrier is formed by the brain endothelial cells coated with basement membrane together with pericytes and astrocyte end-feet facing parenchyma. 33 This barrier is maintained by an elaborate network of tight junctions and adherens junctions that seal gaps between adjacent endothelial cells, 34 resulting in extremely low transcytotic activity.…”

Section: Fabp5 Is Upregulated In Cns Samples From Eae Mice and Ms Pmentioning

confidence: 99%

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The Fabp5/calnexin complex is a prerequisite for sensitization of mice to experimental autoimmune encephalomyelitis

et al. 2020

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We previously showed that calnexin (Canx)-deficient mice are desensitized to experimental autoimmune encephalomyelitis (EAE) induction, a model that is frequently used to study inflammatory demyelinating diseases, due to increased resistance of the blood-brain barrier to immune cell transmigration. We also discovered that Fabp5, an abundant cytoplasmic lipid-binding protein found in brain endothelial cells, makes protein-protein contact with the cytoplasmic C-tail domain of Canx. Remarkably, both Canx-deficient and Fabp5-deficient mice commonly manifest resistance to EAE induction. Here, we evaluated the importance of Fabp5/Canx interactions on EAE pathogenesis and on the patency of a model blood-brain barrier to T-cell transcellular migration. The results demonstrate that formation of a complex comprised of Fabp5 and the C-tail domain of Canx dictates the permeability of the model blood-brain barrier to immune cells and is also a prerequisite for EAE pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Section: Fabp5 Is Upregulated In Cns Samples From Eae Mice and Ms Pmentioning

confidence: 99%

The Fabp5/calnexin complex is a prerequisite for sensitization of mice to experimental autoimmune encephalomyelitis

et al. 2020

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“…Nonetheless, although blood communicates with the brain through the blood–brain barrier, the lymph vessels and the glymphatic system, the interchange is indirect. Therefore, the applicability of blood biomarkers in clinical practice is still not possible due to a series of challenges, in terms of both biological and technical issues [ 60 , 105 , 106 , 107 ]. First, the central nervous system is an isolated environment and the concentration of the potential biomarkers might be relatively low, as they must cross the blood–brain barrier as intact molecules [ 106 ].…”

Section: Blood Biomarkersmentioning

confidence: 99%

Body Fluid Biomarkers for Alzheimer’s Disease—An Up-To-Date Overview

2020

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Neurodegeneration is a highly complex process which is associated with a variety of molecular mechanisms related to ageing. Among neurodegenerative disorders, Alzheimer’s disease (AD) is the most common, affecting more than 45 million individuals. The underlying mechanisms involve amyloid plaques and neurofibrillary tangles (NFTs) deposition, which will subsequently lead to oxidative stress, chronic neuroinflammation, neuron dysfunction, and neurodegeneration. The current diagnosis methods are still limited in regard to the possibility of the accurate and early detection of the diseases. Therefore, research has shifted towards the identification of novel biomarkers and matrices as biomarker sources, beyond amyloid-β and tau protein levels within the cerebrospinal fluid (CSF), that could improve AD diagnosis. In this context, the aim of this paper is to provide an overview of both conventional and novel biomarkers for AD found within body fluids, including CSF, blood, saliva, urine, tears, and olfactory fluids.

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“…More recently, a great deal of attention has been focused on the antibody-independent contribution of B cells [23] and the involvement of Th17 cells in MS evolution [24]. The contribution of Th17 cells takes place in different disease stages including during blood-brain barrier (BBB) permeabilization [25,26].…”

Section: Introductionmentioning

confidence: 99%

Preclinical Therapy with Vitamin D3 in Experimental Encephalomyelitis: Efficacy and Comparison with Paricalcitol

Mimura

Fraga-Silva

Oliveira

et al. 2021

IJMS

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Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS). MS and its animal model called experimental autoimmune encephalomyelitis (EAE) immunopathogenesis involve a plethora of immune cells whose activation releases a variety of proinflammatory mediators and free radicals. Vitamin D3 (VitD) is endowed with immunomodulatory and antioxidant properties that we demonstrated to control EAE development. However, this protective effect triggered hypercalcemia. As such, we compared the therapeutic potential of VitD and paricalcitol (Pari), which is a non-hypercalcemic vitamin D analog, to control EAE. From the seventh day on after EAE induction, mice were injected with VitD or Pari every other day. VitD, but not Pari, displayed downmodulatory ability being able to reduce the recruitment of inflammatory cells, the mRNA expression of inflammatory parameters, and demyelination at the CNS. Lower production of proinflammatory cytokines by lymph node-derived cells and IL-17 by gut explants, and reduced intestinal inflammation were detected in the EAE/VitD group compared to the EAE untreated or Pari groups. Dendritic cells (DCs) differentiated in the presence of VitD developed a more tolerogenic phenotype than in the presence of Pari. These findings suggest that VitD, but not Pari, has the potential to be used as a preventive therapy to control MS severity.

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The action of TH17 cells on blood brain barrier in multiple sclerosis and experimental autoimmune encephalomyelitis

Cited by 66 publications

References 58 publications

The Fabp5/calnexin complex is a prerequisite for sensitization of mice to experimental autoimmune encephalomyelitis

The Fabp5/calnexin complex is a prerequisite for sensitization of mice to experimental autoimmune encephalomyelitis

Body Fluid Biomarkers for Alzheimer’s Disease—An Up-To-Date Overview

Preclinical Therapy with Vitamin D3 in Experimental Encephalomyelitis: Efficacy and Comparison with Paricalcitol

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