• Experimental autoimmune encephalomyelitis
• Immune tolerance
• Multiple sclerosis
• Myelin oligodendrocytes
• Polydopamine nanoparticles

• Animals
• Polymers/chemistry
• Immune Tolerance/drug effects
• Nanoparticles/chemistry
• Multiple Sclerosis/immunology
• Multiple Sclerosis/therapy
• Indoles/chemistry
• Dendritic Cells/immunology
• Vaccines/immunology
• Vaccines/administration & dosage
• Mice
• Autoantigens/immunology
• Female
• T-Lymphocytes, Regulatory/immunology
• Encephalomyelitis, Autoimmune, Experimental/immunology
• Encephalomyelitis, Autoimmune, Experimental/prevention & control
• Mice, Inbred C57BL
• Porosity

• MOGAD
• cognition
• neuroimaging
• neuropsychology
• pediatric

• R01 AI162929 NIAID NIH HHS

• Myelin-Oligodendrocyte Glycoprotein/immunology
• Humans
• Animals
• Autoantibodies/immunology
• Neuromyelitis Optica/immunology
• Autoimmunity/immunology
• Encephalomyelitis, Autoimmune, Experimental/immunology
• Demyelinating Autoimmune Diseases, CNS/immunology

• Acrylamide
• Brain
• Myelin
• Neurodegeneration
• Offspring rat
• Vitamin E

• Humans
• Male
• Pregnancy
• Female
• Rats
• Animals
• Acrylamide/toxicity
• Myelin Sheath
• Vitamin E/pharmacology
• Lactation
• Demyelinating Diseases
• Vitamins/pharmacology

• TDK-2019-1948 Inönü Üniversitesi

• FMRIB Automated Segmentation Tool (FSL-FAST)
• Statistical Parametric Mapping (SPM12)
• cell-based assay
• multiple sclerosis
• myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD)
• volumetric MRI

• Humans
• Myelin-Oligodendrocyte Glycoprotein
• Retrospective Studies
• Cross-Sectional Studies
• Brain/diagnostic imaging
• Brain/pathology
• Gray Matter/pathology
• Multiple Sclerosis/diagnostic imaging
• Multiple Sclerosis/pathology
• Magnetic Resonance Imaging/methods

• None.
• None

• Active immunization
• C57Bl/6, NOD/ShiLt, BALB/c
• Encephalitogenic peptide
• Experimental autoimmune encephalomyelitis (EAE)
• Multiple sclerosis (MS)
• Murine EAE
• Neuroinflammation

• Mice
• Animals
• Multiple Sclerosis/pathology
• Reproducibility of Results
• Encephalomyelitis, Autoimmune, Experimental
• Central Nervous System/pathology
• Myelin Proteins
• Mice, Inbred C57BL
• Mammals

• experimental autoimmune encephalomyelitis (EAE)
• immune tolerance
• lignin nanoparticles
• multiple sclerosis (MS)
• regulatory T cells (Tregs)

• Mice
• Animals
• Multiple Sclerosis/drug therapy
• Nanovaccines
• Lignin/therapeutic use
• Reactive Oxygen Species/therapeutic use
• Encephalomyelitis, Autoimmune, Experimental/drug therapy
• Vaccines
• Mice, Inbred C57BL

• bioinformatics
• differentially expressed genes
• experimental autoimmune encephalomyelitis
• mRNA
• splenocytes

• Mice
• Animals
• Encephalomyelitis, Autoimmune, Experimental/genetics
• Encephalomyelitis, Autoimmune, Experimental/metabolism
• Spleen/pathology
• RNA, Messenger/genetics
• Computational Biology/methods
• Gene Expression Profiling

• T helper cells
• central nervous system
• epigenetics
• experimental autoimmune encephalomyelitis
• histone deacetylases
• multiple sclerosis
• myelin oligodendrocyte glycoprotein
• neutrophils
• tolerance

T cells are a group of lymphocytes that play a central role in the immune system, notably, eliminating pathogens and attacking cancer while being tolerant of the self. Elucidating how immune tolerance is ensured has become a significant research issue for understanding the pathogenesis of autoimmune diseases as well as cancer immunity. T cell immune tolerance is established mainly in the thymic medulla by the removal of self-responsive T cells and the generation of regulatory T cells, this process depends mainly on the expression of a variety of tissue restricted antigens (TRAs) by medullary thymic epithelial cells (mTECs). The expression of TRAs is known to be regulated by at least two independent factors, Fezf2 and Aire, which play non-redundant and complementary roles by different mechanisms. In this review, we introduce the molecular logic of thymic self-antigen expression that underlies T cell selection for the prevention of autoimmunity and the establishment of immune surveillance.

• Aire
• Cancer immunity
• Chd4
• Fezf2
• Immune tolerance
• Regulatory T cells

Myelin oligodendrocyte glycoprotein-IgG-associated disorder (MOGAD) is a nervous system (NS) demyelination disease and a newly recognized distinct disease complicated with various diseases or symptoms; however, MOGAD was once considered a subset of neuromyelitis optica spectrum disorder (NMOSD). The detection of MOG-IgG has been greatly improved by the cell-based assay test method. In one study, 31% of NMOSD patients with negative aquaporin-4 (AQP-4) antibody were MOG-IgG positive. MOGAD occurs in approximately the fourth decade of a person’s life without a markedly female predominance. Usually, optic neuritis (ON), myelitis or acute disseminated encephalomyelitis (ADEM) encephalitis are the typical symptoms of MOGAD. MOG-IgG have been found in patients with peripheral neuropathy, teratoma, COVID-19 pneumonia, etc. Some studies have revealed the presence of brainstem lesions, encephalopathy or cortical encephalitis. Attention should be given to screening patients with atypical symptoms. Compared to NMOSD, MOGAD generally responds well to immunotherapy and has a good functional prognosis. Approximately 44-83% of patients undergo relapsing episodes within 8 months, which mostly involve the optic nerve, and persistently observed MOG-IgG and severe clinical performance may indicate a polyphasic course of illness. Currently, there is a lack of clinical randomized controlled trials on the treatment and prognosis of MOGAD. The purpose of this review is to discuss the clinical manifestations, imaging features, outcomes and prognosis of MOGAD.

• National Natural Science Foundation of China

• animal models
• autoimmunity
• experimental autoimmune encephalomyelitis
• multiple sclerosis

• Annualized relapse rate
• Meta-analysis
• Myelin oligodendrocyte glycoprotein
• Rituximab

Purpose: To evaluate the clinical differences between pediatric and adult patients with myelin oligodendrocyte glycoprotein antibody-associated encephalomyelitis (MOG-EM).

Methods: We retrospectively reviewed the clinical features of pediatric and adult patients with MOG-EM in our center between November 2015 and October 2020.

Results: Twenty-eight pediatric patients and 25 adults were admitted to our study. Bilateral optic neuritis (BON) was the most common initial phenotype in the pediatric group but less common in the adult group (28.57 vs. 0%, p = 0.0119). Almost half of the adult patients presented with neuromyelitis optica spectrum disease (NMOSD), which was less prevalent among the pediatrics (48 vs. 21.43%, p = 0.0414). Visual impairment was the most common symptom in both groups during the initial attack (pediatric group, 39.29%; adult group, 64%) and throughout the full course (pediatric group, 57.14%; adult group, 72%). More pediatric patients suffered from fever than adult patients at onset (pediatric group, 28.57%; adult group, 4%; p = 0.0442) and throughout the full course (pediatric group, 39.29%; adult group, 12%; p = 0.0245). Multiple patchy lesions in subcortical white matter (pediatric group, 40.74%; adult group, 45%), periventricular (pediatric group, 25.93%; adult group, 35%), infratentorial (pediatric group, 18.52%; adult group, 30%) and deep gray matter (pediatric group, 25.93%; adult group, 20%) were frequent in all cases, no significant difference was found between the two groups, while bilateral optic nerve involvement was more frequent in pediatric group (61.54 vs. 14.29%, p = 0.0042) and unilateral optic nerve involvement was higher in adult group (64.29 vs. 15.38%, p = 0.0052). At the last follow-up, adult patients had a higher average EDSS score (median 1.0, range 0–3) than pediatrics (median 0.0, range 0–3), though not significant (p = 0.0752). Patients aged 0–9 years (61.54%) and 10–18 years (70%), and patients presenting with encephalitis/meningoencephalitis (100%) and ADEM (75%) were more likely to recover fully.

Conclusions: Visual impairment was the dominant symptom in both pediatric and adult patients, while fever was more frequent in pediatric patients. Data suggested that BON and bilateral optic nerve involvement were more common in pediatric cases whereas NMOSD and unilateral optic nerve involvement were more prevalent in adults. The younger patients and patients presenting with encephalitis/meningoencephalitis and ADEM tended to recover better.

• adults
• demyelinating disease
• myelin oligodendrocyte glycoprotein antibody-associated encephalomyelitis
• optic neuritis
• pediatrics

Despite progress in treating relapsing multiple sclerosis (MS), effective inhibition of nonrelapsing progressive MS is an urgent, unmet, clinical need. Animal models of MS, such as experimental autoimmune encephalomyelitis (EAE), provide valuable tools to examine the mechanisms contributing to disease and may be important for developing rational therapeutic approaches for treatment of progressive MS. It has been suggested that myelin oligodendrocyte glycoprotein (MOG) peptide residues 35‐55 (MOG^35‐55)‐induced EAE in nonobese diabetic (NOD) mice resembles secondary progressive MS. The objective was to determine whether the published data merits such claims.

Induction and monitoring of EAE in NOD mice and literature review.

It is evident that the NOD mouse model lacks validity as a progressive MS model as the individual course seems to be an asynchronous, relapsing‐remitting neurodegenerative disease, characterized by increasingly poor recovery from relapse. The seemingly progressive course seen in group means of clinical score is an artifact of data handling and interpretation.

Although MOG^35‐55‐induced EAE in NOD mice may provide some clues about approaches to block neurodegeneration associated with the inflammatory penumbra as lesions form, it should not be used to justify trials in people with nonactive, progressive MS. This adds further support to the view that drug studies in animals should universally adopt transparent raw data deposition as part of the publication process, such that claims can adequately be interrogated. This transparency is important if animal‐based science is to remain a credible part of translational research in MS.

• antibody(s)
• immune response(s)
• immunogenicity
• immunology
• pharmacodynamics
• pharmacokinetics
• protein(s)

• Animals
• Antibodies/immunology
• Antibody Formation/drug effects
• Antibody Formation/immunology
• Humans
• Proteins/immunology
• Proteins/pharmacology

• R01 HL070227 NHLBI NIH HHS

• Amyloid
• multiple sclerosis
• myelin
• oxidative stress

Dendritic cells (DC) are professional antigen presenting cells that have a key role in shaping the immune response. Tolerogenic DC (tolDC) have immuno-regulatory properties and they are a promising prospective therapy for multiple sclerosis and other autoimmune diseases. Ethyl pyruvate (EP) is a redox analog of dimethyl fumarate (Tecfidera), a drug for multiple sclerosis treatment. We have recently shown that EP ameliorates experimental autoimmune encephalomyelitis, a multiple sclerosis murine model. Here, we expanded our study to its tolerogenic effects on DC. Phenotypic analysis has shown that DC obtained from mice or humans reduce expression of molecules required for T cell activation such as CD86, CD83, and HLA-DR under the influence of EP, while CD11c expression and viability of DC are not affected. Furthermore, EP-treated DC restrain proliferation and modulate cytokine production of allogeneic lymphocytes. These results demonstrate that EP has the ability to direct DC toward tolDC.

• autoimmunity
• dendritic cells
• ethyl pyruvate
• immune-regulation
• tolerogenicity

• Multiple sclerosis
• myelin repair
• oligodendroglia
• therapy
• trials

• Animals
• Humans
• Multiple Sclerosis/drug therapy
• Oligodendroglia/drug effects
• Remyelination/drug effects

• R01 NS096148 NINDS NIH HHS

• Cerebrospinal fluid (CSF)
• MRI
• Multiple sclerosis (MS)
• Myelin oligodendrocyte glycoprotein (MOG) antibodies
• Neuromyelitis optica (NMO)
• Optic neuritis (ON)

• Alzheimer’s disease
• Demyelination
• Myelin
• Neurodegenerative diseases
• Oligodendrocyte

• EAE
• ethidium bromide
• glial cells
• lysolecithin toxin and virus-induced demyelination
• multiple sclerosis

Susceptibility to autoimmune diseases results from the encounter of a complex and long evolved genetic context with a no less complex and changing environment. Major actors in maintaining health are regulatory T cells (Treg) that primarily dampen a large subset of autoreactive lymphocytes escaping thymic negative selection. Here, we directly asked whether Treg participate in defining susceptibility and resistance to Experimental Autoimmune Prostatitis (EAP). We analyzed three common laboratory strains of mice presenting with different susceptibility to autoimmune prostatitis upon immunization with prostate proteins. The NOD, the C57BL/6 and the BALB/c mice that can be classified along a disease score ranging from severe, mild and to undetectable, respectively. Upon mild and transient depletion of Treg at the induction phase of EAP, each model showed an increment along this score, most remarkably with the BALB/c mice switching from a resistant to a susceptible phenotype. We further show that disease associates with the upregulation of CXCR3 expression on effector T cells, a process requiring IFNγ. Together with recent advances on environmental factors affecting Treg, these findings provide a likely cellular and molecular explanation to the recent rise in autoimmune diseases incidence.

• EAE
• Treg
• anti-inflammatory
• mice
• microglia

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterized by inflammation, demyelination and axonal pathology. Myelin basic protein/proteolipid protein (MBP-PLP) fusion protein MP4 is capable of inducing chronic experimental autoimmune encephalomyelitis (EAE) in susceptible mouse strains mirroring diverse histopathological and immunological hallmarks of MS. Limited availability of human tissue underscores the importance of animal models to study the pathology of MS.

Twenty-two female C57BL/6 (B6) mice were immunized with MP4 and the clinical development of experimental autoimmune encephalomyelitis (EAE) was observed. Methylene blue-stained semi-thin and ultra-thin sections of the lumbar spinal cord were assessed at the peak of acute EAE, three months (chronic EAE) and six months after onset of EAE (long-term EAE). The extent of lesional area and inflammation were analyzed in semi-thin sections on a light microscopic level. The magnitude of demyelination and axonal damage were determined using electron microscopy. Emphasis was put on the ventrolateral tract (VLT) of the spinal cord.

B6 mice demonstrated increasing demyelination and severe axonal pathology in the course of MP4-induced EAE. In addition, mitochondrial swelling and a decrease in the nearest neighbor neurofilament distance (NNND) as early signs of axonal damage were evident with the onset of EAE. In semi-thin sections we observed the maximum of lesional area in the chronic state of EAE while inflammation was found to a similar extent in acute and chronic EAE. In contrast to the well-established myelin oligodendrocyte glycoprotein (MOG) model, disease stages of MP4-induced EAE could not be distinguished by assessing the extent of parenchymal edema or the grade of inflammation.

Our results complement our previous ultrastructural studies of B6 EAE models and suggest that B6 mice immunized with different antigens constitute useful instruments to study the diverse histopathological aspects of MS.

• Animals
• Axons/pathology
• Axons/ultrastructure
• Demyelinating Diseases
• Disease Models, Animal
• Disease Progression
• Encephalomyelitis, Autoimmune, Experimental/chemically induced
• Encephalomyelitis, Autoimmune, Experimental/immunology
• Encephalomyelitis, Autoimmune, Experimental/pathology
• Encephalomyelitis, Autoimmune, Experimental/physiopathology
• Female
• Humans
• Immunization
• Lumbar Vertebrae/pathology
• Lumbar Vertebrae/ultrastructure
• Mice
• Mice, Inbred C57BL
• Microtomy
• Mitochondria/pathology
• Mitochondria/ultrastructure
• Mitochondrial Swelling
• Multiple Sclerosis/immunology
• Multiple Sclerosis/pathology
• Multiple Sclerosis/physiopathology
• Myelin Basic Protein/administration & dosage
• Myelin Proteolipid Protein/administration & dosage
• Myelin Sheath/pathology
• Myelin Sheath/ultrastructure
• Recombinant Fusion Proteins/administration & dosage
• Severity of Illness Index
• Time Factors

• antibodies
• enzyme-linked immunosorbent assay
• epitope mapping
• experimental autoimmune encephalomyelitis
• microwave-assisted solid-phase synthesis
• myelin oligodendrocyte glycoprotein

Multiple sclerosis (MS) is an inflammatory/autoimmune disease of the central nervous system (CNS) mainly mediated by myelin specific T cells. It is widely believed that environmental factors, including fungal infections, contribute to disease induction or evolution. Even though Candida infection among MS patients has been described, the participation of this fungus in this pathology is not clear. The purpose of this work was to evaluate the effect of a Candida albicans infection on experimental autoimmune encephalomyelitis (EAE) that is a widely accepted model to study MS. Female C57BL/6 mice were infected with C. albicans and 3 days later, animals were submitted to EAE induction by immunization with myelin oligodendrocyte glycoprotein. Previous infection increased the clinical score and also the body weight loss. EAE aggravation was associated with expansion of peripheral CD4⁺ T cells and production of high levels of TNF-α, IFN-γ IL-6, and IL-17 by spleen and CNS cells. In addition to yeast and hyphae, fungus specific T cells were found in the CNS. These findings suggest that C. albicans infection before EAE induction aggravates EAE, and possibly MS, mainly by CNS dissemination and local induction of encephalitogenic cytokines. Peripheral production of encephalitogenic cytokines could also contribute to disease aggravation.

• Acrylamides/administration & dosage
• Acrylamides/pharmacokinetics
• Acrylamides/pharmacology
• Active Transport, Cell Nucleus/drug effects
• Animals
• Axons/drug effects
• Axons/metabolism
• Axons/pathology
• Cell Nucleus/metabolism
• Cells, Cultured
• Disease Models, Animal
• Disease Progression
• Drug Evaluation, Preclinical
• Encephalomyelitis, Autoimmune, Experimental/drug therapy
• Female
• Karyopherins/antagonists & inhibitors
• Karyopherins/genetics
• Karyopherins/metabolism
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Neuroprotective Agents/administration & dosage
• Neuroprotective Agents/pharmacokinetics
• Neuroprotective Agents/pharmacology
• Proteomics
• Rats
• Rats, Sprague-Dawley
• Receptors, Cytoplasmic and Nuclear/antagonists & inhibitors
• Receptors, Cytoplasmic and Nuclear/genetics
• Receptors, Cytoplasmic and Nuclear/metabolism
• Thiazoles/administration & dosage
• Thiazoles/pharmacokinetics
• Thiazoles/pharmacology
• Treatment Outcome
• Exportin 1 Protein

• R37-NS42925 NINDS NIH HHS
• R01-NS69385 NINDS NIH HHS
• R01 NS052738 NINDS NIH HHS
• R01 AI088106 NIAID NIH HHS
• R01 NS069835 NINDS NIH HHS
• R01 AI068963 NIAID NIH HHS
• R37 NS042925 NINDS NIH HHS
• R01 GM069909 NIGMS NIH HHS

To optimize sensitivity and disease specificity of a myelin oligodendrocyte glycoprotein (MOG) antibody assay.

Consecutive sera (n = 1,109) sent for aquaporin-4 (AQP4) antibody testing were screened for MOG antibodies (Abs) by cell-based assays using either full-length human MOG (FL-MOG) or the short-length form (SL-MOG). The Abs were initially detected by Alexa Fluor goat anti-human IgG (H + L) and subsequently by Alexa Fluor mouse antibodies to human IgG1.

When tested at 1:20 dilution, 40/1,109 sera were positive for AQP4-Abs, 21 for SL-MOG, and 180 for FL-MOG. Only one of the 40 AQP4-Ab–positive sera was positive for SL-MOG-Abs, but 10 (25%) were positive for FL-MOG-Abs (p = 0.0069). Of equal concern, 48% (42/88) of sera from controls (patients with epilepsy) were positive by FL-MOG assay. However, using an IgG1-specific secondary antibody, only 65/1,109 (5.8%) sera were positive on FL-MOG, and AQP4-Ab– positive and control sera were negative. IgM reactivity accounted for the remaining anti-human IgG (H + L) positivity toward FL-MOG. The clinical diagnoses were obtained in 33 FL-MOG–positive patients, blinded to the antibody data. IgG1-Abs to FL-MOG were associated with optic neuritis (n = 11), AQP4-seronegative neuromyelitis optica spectrum disorder (n = 4), and acute disseminated encephalomyelitis (n = 1). All 7 patients with probable multiple sclerosis (MS) were MOG-IgG1 negative.

The limited disease specificity of FL-MOG-Abs identified using Alexa Fluor goat anti-human IgG (H + L) is due in part to detection of IgM-Abs. Use of the FL-MOG and restricting to IgG1-Abs substantially improves specificity for non-MS demyelinating diseases.

This study provides Class II evidence that the presence of serum IgG1- MOG-Abs in AQP4-Ab–negative patients distinguishes non-MS CNS demyelinating disorders from MS (sensitivity 24%, 95% confidence interval [CI] 9%–45%; specificity 100%, 95% CI 88%–100%).

MBP(85–99), an immuno-dominant epitope of myelin basic protein which binds to the major histocompatibility complex haplotype HLA-DR2 is widely implicated in the pathogenesis of multiple sclerosis. J5, an antagonist of MBP(85–99), that blocks the binding of MBP(85–99) to soluble HLA-DR2b much more efficiently than glatiramer acetate (a random copolymer comprising major MHC and T-cell receptor contact residues), was transformed into analogs with superior biological half-lives and antagonistic-activities by substitution of some of its residues with homo-β-amino acids. S18, the best analog obtained ameliorated symptoms of experimental autoimmune encephalomyelitis at least twice more effectively than glatiramer acetate or J5. S18 displayed marked resistance to proteolysis in-vitro; biological impact of which was evident in the form of delayed clinical onset of disease and prolonged therapeutic-benefits. Besides active suppression of MBP(85–99)-reactive CD4⁺ T-cells in-vitro and in-vivo S18 treatment also generated IL-4 producing CD4⁺ T-cell clones, through which protective effect could be transferred passively.

• CNS demyelinating disease
• Chronic-relapsing EAE
• EAE
• EAE variant
• MOG
• MS model
• NOD/Lt mouse strain
• Neurodegenerative disease
• Neuroinflammation
• Spatio-temporal lesion mapping

• Animals
• Disease Models, Animal
• Encephalomyelitis, Autoimmune, Experimental/genetics
• Mice
• Mice, Inbred NOD/genetics
• Multiple Sclerosis/genetics
• Myelin-Oligodendrocyte Glycoprotein
• Peptide Fragments

• Antibodies
• Autoimmune disease
• B cells
• Epitope spreading

• Apolipoprotein A-I
• EAE
• Multiple sclerosis
• Neurological disease

• Altered peptide ligands
• Beta-amino acid
• Immunosuppressive
• Multiple sclerosis
• Myelin oligodendrocyte glycoprotein
• Neuroinflammation

Studies evaluating T-cell recognition of myelin oligodendrocyte glycoprotein (MOG) in multiple sclerosis (MS) and its model, experimental autoimmune encephalomyelitis (EAE), have focused mostly on its 117 amino acid (aa) extracellular domain, especially peptide (p) 35-55. We characterized T-cell responses to the entire 218 aa MOG sequence, including its transmembrane and cytoplasmic domains.

T-cell recognition in mice was examined using overlapping peptides and intact full-length mouse MOG. EAE was evaluated by peptide immunization and by adoptive transfer of MOG epitope-specific T cells. Frequency of epitope-specific T cells was examined by ELISPOT.

Three T-cell determinants of MOG were discovered in its transmembrane and cytoplasmic domains, p119–132, p181–195, and p186–200. Transmembrane MOG p119-132 induced clinical EAE, CNS inflammation, and demyelination as potently as p35-55 in C57BL/6 mice and other H-2^b strains. p119-128 contained its minimal encephalitogenic epitope. p119-132 did not cause disease in EAE-susceptible non-H-2^b strains, including Biozzi, NOD, and PL/J. MOG p119-132–specific T cells produced Th1 and Th17 cytokines and transferred EAE to wild-type recipient mice. After immunization with full-length MOG, a significantly higher frequency of MOG-reactive T cells responded to p119-132 than to p35-55, demonstrating that p119-132 is an immunodominant encephalitogenic epitope. MOG p181-195 did not cause EAE, and MOG p181-195–specific T cells could not transfer EAE into wild-type or highly susceptible T- and B-cell–deficient mice.

Transmembrane and cytoplasmic domains of MOG contain immunodominant T-cell epitopes in EAE. A CNS autoantigen can also contain nonpathogenic stimulatory T-cell epitopes. Recognition that a myelin antigen contains multiple encephalitogenic and nonencephalitogenic determinants may have implications for therapeutic development in MS.

• CC chemokine ligand 2 (CCL2)
• Chronic relapsing–remitting experimental autoimmune encephalomyelitis (CREAE)
• Interferon-γ (IFN-γ)
• Interleukin-6 (IL-6)
• Multiple sclerosis
• Tumor necrosis factor-α (TNF-α)

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) and is characterized by the destruction of myelin and axons leading to progressive disability. Peptide epitopes from CNS proteins, such as myelin oligodendrocyte glycoprotein (MOG), possess promising immunoregulatory potential for treating MS; however, their instability and poor bioavailability is a major impediment for their use clinically. To overcome this problem, we used molecular grafting to incorporate peptide sequences from the MOG_35–55 epitope onto a cyclotide, which is a macrocyclic peptide scaffold that has been shown to be intrinsically stable. Using this approach, we designed novel cyclic peptides that retained the structure and stability of the parent scaffold. One of the grafted peptides, MOG3, displayed potent ability to prevent disease development in a mouse model of MS. These results demonstrate the potential of bioengineered cyclic peptides for the treatment of MS.

• CMV981-1003
• Cytomegalovirus
• EB virus DNA polymerase 627-641
• EBV627-641
• Lewis rat
• Molecular mimicry
• Multiple sclerosis
• Myelin basic protein
• Myelin oligodendroglia glycoprotein
• cytomegalovirus major capsid protein UL86 981-1003

The potential role of Nogo-66 Receptor 1 (NgR1) on immune cell phenotypes and their activation during neuroinflammatory diseases such as multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), is unclear. To further understand the function of this receptor on haematopoietically-derived cells, phenotypic and functional analyses were performed using NgR1-deficient (ngr1-/-) animals. Flow cytometry-based phenotypic analyses performed on blood, spleen, thymus, lymph nodes, bone marrow and central nervous-system (CNS)-infiltrating blood cells revealed no immunological defects in naïve ngr1-/- animals versus wild-type littermate (WTLM) controls. EAE was induced by either recombinant myelin oligodendrocyte glycoprotein (rMOG), a model in which B cells are considered to contribute pathogenically, or by MOG_35–55 peptide, a B cell-independent model. We have demonstrated that in ngr1-/- mice injected with MOG_35–55, a significant reduction in the severity of EAE correlated with reduced axonal damage present in the spinal cord when compared to their WTLM controls. However, despite a reduction in axonal damage observed in the CNS of ngr1-/- mice at the chronic stage of disease, no clinical differences could be attributed to a specific genotype when rMOG was used as the encephalitogen. Following MOG_35–55-induction of EAE, we could not derive any major changes to the immune cell populations analyzed between ngr1-/- and WTLM mice. Collectively, these data demonstrate that NgR1 has little if any effects on the repertoire of immune cells, their activation and trafficking to the CNS.

• Animals
• B-Lymphocytes/immunology
• B-Lymphocytes/pathology
• Cell Movement/genetics
• Cell Movement/immunology
• Central Nervous System/immunology
• Central Nervous System/pathology
• Encephalomyelitis, Autoimmune, Experimental/genetics
• Encephalomyelitis, Autoimmune, Experimental/immunology
• Encephalomyelitis, Autoimmune, Experimental/pathology
• GPI-Linked Proteins/genetics
• GPI-Linked Proteins/immunology
• Lymphocyte Activation/genetics
• Mice
• Mice, Knockout
• Multiple Sclerosis/genetics
• Multiple Sclerosis/immunology
• Multiple Sclerosis/pathology
• Myelin Proteins/genetics
• Myelin Proteins/immunology
• Nogo Receptor 1
• Receptors, Cell Surface/genetics
• Receptors, Cell Surface/immunology

• EAE
• IL-10
• Multiple sclerosis
• TLR7
• Treg cell