scholarly journals B cell-mediated immunomodulation by S-nitrosoglutathione (GSNO) in experimental autoimmune encephalomyelitis

2020 ◽  
Author(s):  
Judong Kim ◽  
S.M. Touhidul Islam ◽  
Jeseong Won ◽  
Avtar K. Singh ◽  
Inderjit Singh
Keyword(s):  
B Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
B Cell ◽  
Cell Function ◽  
Autoimmune Encephalomyelitis ◽  
Immune Balance ◽  
Eae Model ◽  
Experimental Autoimmune

Abstract Background Experimental autoimmune encephalomyelitis (EAE) is the most commonly used animal model for human multiple sclerosis (MS), a demyelinating autoimmune disease mediated by T and B lymphocytes. The aim of the present study was to investigate the role of S-nitrosoglutathione (GSNO), a physiological nitric oxide carrier molecule, in regulation of effector or regulatory B cell function as IL-6 and IL-10 expressions and thus the potential role of GSNO in targeting B cell-mediated immunopathogenesis in MS using EAE model. Methods To this purpose, the in vivo EAE mouse model, generated by immunization with myelin oligodendrocyte glycoprotein (MOG) 35-55 peptide, or in vitro model of cultured B cells stimulated with lipopolysaccharide or anti-IgM antibody were treated with exogenous GSNO or N6022, an inhibitor of GSNO reductase (GSNOR; GSNO degrading enzyme) to increase endogenous GSNO, and then analyzed for B cell specific IL-6 and IL-10 expression. Results In EAE model, administration of exogenous GSNO or inhibition of endogenous GSNO catabolism by N6022 treatment ameliorated the clinical disease with decreased CNS infiltration of B cells. In addition, GSNO/N6022 treatments increased the number of IL-10+ B cells but decreased the number of IL-6+ B cells in the CNS and spleen. Accordingly, GSNO/N6022 treatments increased the expression of IL-10 while reducing the IL-6 expression in the blood. Similar observations were also made in in vitro B cell culture model where GSNO treatment increased the IL-10+ B cells but decreased the IL-6+ B cells under BCR or TLR4 stimulatory conditions and under CD40 and BAFF co-stimulatory conditions. Accordingly, GSNO treatment increased the B cell production of IL-10 but reduced the IL-6 production under both stimulatory and co-stimulatory conditions. In vitro stimulation and co-stimulation of cultured naïve B cells increased two major distinct B cell populations; CD1dlow CD5high and CD1dhigh CD5high. In both populations, GSNO treatment increased the number of IL-10+ cells but decreased the IL-6+ cells. Conclusion These data document, for the first time, that cellular GSNO homeostasis is a critical target for the regulation of IL-10+ B cells vs. IL-6+ B cells mediated immune balance under auto-immune disease conditions.

scholarly journals Hormones in experimental autoimmune encephalomyelitis (EAE) animal models

2021 ◽  
Vol 12 (1) ◽  
pp. 164-189
Author(s):  
Majid Ghareghani ◽  
Amir Ghanbari ◽  
Ali Eid ◽  
Abdullah Shaito ◽  
Wael Mohamed ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Demyelinating Disease ◽  
Endocrine System ◽  
Laboratory Animals ◽  
Autoimmune Encephalomyelitis ◽  
Eae Model ◽  
Experimental Autoimmune

Abstract Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) in which activated immune cells attack the CNS and cause inflammation and demyelination. While the etiology of MS is still largely unknown, the interaction between hormones and the immune system plays a role in disease progression, but the mechanisms by which this occurs are incompletely understood. Several in vitro and in vivo experimental, but also clinical studies, have addressed the possible role of the endocrine system in susceptibility and severity of autoimmune diseases. Although there are several demyelinating models, experimental autoimmune encephalomyelitis (EAE) is the oldest and most commonly used model for MS in laboratory animals which enables researchers to translate their findings from EAE into human. Evidences imply that there is great heterogeneity in the susceptibility to the induction, the method of induction, and the response to various immunological or pharmacological interventions, which led to conflicting results on the role of specific hormones in the EAE model. In this review, we address the role of endocrine system in EAE model to provide a comprehensive view and a better understanding of the interactions between the endocrine and the immune systems in various models of EAE, to open up a ground for further detailed studies in this field by considering and comparing the results and models used in previous studies.

scholarly journals TCDD Inhibition of IgG1 Production in Experimental Autoimmune Encephalomyelitis (EAE) and In Vitro

Antibodies ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 4
Author(s):  
Ashleigh J. Nicaise ◽  
Amye McDonald ◽  
Erin Rushing Sears ◽  
Trell Sturgis ◽  
Barbara L. F. Kaplan
Keyword(s):  
B Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Autoimmune Encephalomyelitis ◽  
Aryl Hydrocarbon ◽  
Eae Model ◽  
Igg1 Subclass ◽  
Experimental Autoimmune

The environmental contaminant 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) is a ligand for the aryl hydrocarbon receptor (AhR). TCDD is well-characterized to produce immunotoxicity, including suppression of antibody production. Previously we showed that TCDD inhibited myelin oligodendrocyte glycoprotein (MOG) peptide-specific IgG and attenuated disease in experimental autoimmune encephalomyelitis (EAE) model in mice. Thus, the purpose of this study was to characterize the effects of TCDD on IgG subclasses in EAE and in vitro and assess effects in B cells derived from various tissues. TCDD modestly suppressed intracellular IgG expression in splenocytes (SPLC), but not bone marrow (BM) or lymph node (LN) cells. To further understand TCDD’s effects on IgG, we utilized LPS and LPS + IL-4 in vitro to stimulate IgG3 and IgG1 production, respectively. TCDD preferentially suppressed IgG1+ cell surface expression, especially in SPLC. However, TCDD was able to suppress IgG1 and IgG3 secretion from SPLC and B cells, but not BM cells. Lastly, we revisited the EAE model and determined that TCDD suppressed MOG-specific IgG1 production. Together these data show that the IgG1 subclass of IgG is a sensitive target of suppression by TCDD. Part of the pathophysiology of EAE involves production of pathogenic antibodies that can recruit cytolytic cells to destroy MOG-expressing cells that comprise myelin, so inhibition of IgG1 likely contributes to TCDD’s EAE disease attenuation.

scholarly journals An essential role of virus-infected B cells in the marmoset experimental autoimmune encephalomyelitis model

2017 ◽  
Vol 3 (1) ◽  
pp. 205521731769018 ◽  
Author(s):  
Bert A ’t Hart ◽  
Yolanda S Kap
Keyword(s):  
B Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Epstein Barr Virus ◽  
Infection Prevalence ◽  
Autoimmune Encephalomyelitis ◽  
Barr Virus ◽  
Experimental Autoimmune Encephalomyelitis Model ◽  
Epstein Barr ◽  
Experimental Autoimmune

Infection with Epstein–Barr virus (EBV) has been associated with an enhanced risk of genetically susceptible individuals to develop multiple sclerosis (MS). However, an explanation for the contrast between the high EBV infection prevalence (60–90%) and the low MS prevalence (0.1%) eludes us. Here we propose a new concept for the EBV–MS association developed in the experimental autoimmune encephalomyelitis model in marmoset monkeys, which are naturally infected with the EBV-related γ1-herpesvirus CalHV3. The data indicate that the infection of B cells with a γ1-herpesvirus endows them with the capacity to activate auto-aggressive CD8+ T cells specific for myelin oligodendrocyte glycoprotein.

scholarly journals Experimental Autoimmune Encephalomyelitis Induction in Genetically B Cell–deficient Mice

1996 ◽  
Vol 184 (6) ◽  
pp. 2271-2278 ◽  
Author(s):  
Susan D. Wolf ◽  
Bonnie N. Dittel ◽  
Fridrika Hardardottir ◽  
Charles A. Janeway
Keyword(s):  
T Cells ◽  
B Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
B Cell ◽  
Immune Modulation ◽  
Disease Onset ◽  
Central Nervous System Disease ◽  
Autoimmune Encephalomyelitis ◽  
Deficient Mice ◽  
Experimental Autoimmune

Experimental autoimmune encephalomyelitis (EAE) is an animal model for autoimmune central nervous system disease mediated by CD4 T cells. To examine the role of B cells in the induction of EAE, we used B10.PL (I-Au) mice rendered deficient in B cells by deletion of their μ chain transmembrane region (B10.PLμMT). By immunizing B10.PL and B10.PLμMT mice with the NH-terminal myelin basic protein encephalitogenic peptide Ac1-11, we observed no difference in the onset or severity of disease in the absence of mature B cells. There was, however, a greater variation in disease onset, severity, and especially of recovery in the B cell–deficient mice compared to controls. B10.PLμMT mice rarely returned to normal in the absence of B cells. Taken together, our data suggest that B cells do not play a role in the activation of encephalitogenic T cells, but may contribute to the immune modulation of acute EAE. The mechanisms to explain these effects are discussed.

scholarly journals Cordycepin Prevents and Ameliorates Experimental Autoimmune Encephalomyelitis by Inhibiting Leukocyte Infiltration and Reducing Neuroinflammation

2021 ◽  
Author(s):  
Ying-Chyi Song ◽  
Chuan-Teng Liu ◽  
Hui-Ju Lee ◽  
Hung-Rong Yen
Keyword(s):  
Dendritic Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
T Cell Subsets ◽  
Microglial Cells ◽  
Mouse Bone Marrow ◽  
Therapeutic Effects ◽  
Autoimmune Encephalomyelitis ◽  
Eae Model ◽  
Experimental Autoimmune

Abstract BackgroundMultiple sclerosis (MS) is a neuroinflammatory autoimmune disease characterized by multifocal perivascular infiltration of immune cells in the central nervous system (CNS). Current treatment for MS is unsatisfactory, and we aimed to search for immunomodulatory agents from bioactive constituents of natural origin. Cordycepin (3'-deoxyadenosine), an adenosine analogue initially extracted from the fungus Cordyceps militarisa, is one of the candidates that has multiple actions. However, its effect on MS is unknown.MethodsWe first investigated the in vitro effects of cordycepin on mouse and human dendritic cells, microglial cells, macrophages, and T cell subsets. Cordycepin was administered to the experimental autoimmune encephalomyelitis (EAE) model at various time points to evaluate the effects in preventive and therapeutic model. Chemokine array and next-generation sequencing (NGS) were applied to identify the key molecules and genes involved in the mechanism. ResultsCordycepin attenuated the activation of LPS-induced mouse bone marrow-derived dendritic cells (BMDCs) and human monocyte-derived dendritic cells (MoDCs) through the inhibition of the AKT, ERK, NF-κB, and ROS pathways and impaired the migration of BMDCs through the downregulation of adhesion molecules and chemokine receptors in vitro. In EAE model, preventive treatment with cordycepin decreased the expression of trafficking factors in the CNS, inhibited the secretion of inflammatory cytokines (IFN-g , IL-6, TNF-a, and IL-17) induced by specific peptides, and attenuated clinical symptoms. A chemokine array indicated that cordycepin treatment reversed the high levels of CCL6, PARRES2, IL-16, CXCL10, and CCL12 in the brain and spinal cord of EAE mice, consistent with the RNA-seq data. Moreover, cordycepin suppressed the release of neuroinflammatory cytokines by activated microglial cells, macrophages, Th17 cells, Tc1 cells, and Th1 cells in vitro. Furthermore, cordycepin treatment exerted therapeutic effects on attenuating the clinical disease severity in the early disease onset stage and late disease progression stage. ConclusionsOur study suggests that cordycepin treatment may not only prevent the occurrence of MS by inhibiting DC activation and migration but also potentially ameliorates the progression of MS by reducing neuroinflammation, which may provide insights into the development of new approaches for the treatment of MS.

scholarly journals Regulatory Role of Peritoneal B Cells in EAE

2016 ◽  
Vol 17 (2) ◽  
pp. 87-92
Author(s):  
Bojana Stojanović ◽  
Jelena Milovanović ◽  
Aleksandar Arsenijević ◽  
Marija Milovanovic ◽  
Miodrag L. Lukic
Keyword(s):  
Multiple Sclerosis ◽  
B Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Regulatory Role ◽  
Disease Development ◽  
Regulatory B Cells ◽  
Autoimmune Encephalomyelitis ◽  
Inflammatory Stimuli ◽  
Experimental Autoimmune

Abstract B cells play a dual role in the pathogenesis of autoimmune diseases. In experimental autoimmune encephalomyelitis (EAE), an experimental model for multiple sclerosis, B cells contribute to disease progression, while their regulatory role predominates in the initial phases of disease development. Several studies have identified different subsets of regulatory B cells, mostly in the spleen, which are all sources of IL-10. However, peritoneal regulatory B cells are also important producers of IL-10, can migrate towards inflammatory stimuli, and could have an immunoregulatory function. As we have observed expansion of regulatory B cells in the peritoneum of resistant mice after EAE induction, herein we discuss the regulatory roles of B cells in EAE pathogenesis and the possible role of peritoneal regulatory B cells in resistance to EAE induction.

scholarly journals Cnp Promoter-Driven Sustained ERK1/2 Activation Increases B-Cell Activation and Suppresses Experimental Autoimmune Encephalomyelitis

ASN NEURO ◽  
2020 ◽  
Vol 12 ◽  
pp. 175909142097191
Author(s):  
Marisa A. Jeffries ◽  
Alison E. Obr ◽  
Kelly Urbanek ◽  
Sharyl L. Fyffe-Maricich ◽  
Teresa L. Wood
Keyword(s):  
T Cells ◽  
B Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
B Cell ◽  
Active Form ◽  
Fold Increase ◽  
Clinical Severity ◽  
Autoimmune Encephalomyelitis ◽  
Immune Mediated ◽  
Experimental Autoimmune

The ERK1/2 signaling pathway promotes myelin wrapping during development and remyelination, and sustained ERK1/2 activation in the oligodendrocyte (OL) lineage results in hypermyelination of the CNS. We therefore hypothesized that increased ERK1/2 signaling in the OL lineage would 1) protect against immune-mediated demyelination due to increased baseline myelin thickness and/or 2) promote enhanced remyelination and thus functional recovery after experimental autoimmune encephalomyelitis (EAE) induction. Cnp-Cre;Mek1DD-eGFP/+ mice that express a constitutively active form of MEK1 (the upstream activator of ERK1/2) in the OL lineage, exhibited a significant decrease in EAE clinical severity compared to controls. However, experiments using tamoxifen-inducible Plp-CreERT;Mek1DD-eGFP/+ or Pdgfrα-CreERT;Mek1DD-eGFP mice revealed this was not solely due to a protective or reparative effect resulting from MEK1DD expression specifically in the OL lineage. Because EAE is an immune-mediated disease, we examined Cnp-Cre; Mek1DD-eGFP/+ splenic immune cells for recombination. Surprisingly, GFP+ recombined CD19+ B-cells, CD11b+ monocytes, and CD3+ T-cells were noted when Cre expression was driven by the Cnp promoter. While ERK1/2 signaling in monocytes and T-cells is associated with proinflammatory activation, fewer studies have examined ERK1/2 signaling in B-cell populations. After in vitro stimulation, MEK1DD-expressing B-cells exhibited a 3-fold increase in CD138+ plasmablasts and a 5-fold increase in CD5+CD1dhi B-cells compared to controls. Stimulated MEK1DD-expressing B-cells also exhibited an upregulation of IL-10, known to suppress the initiation of EAE when produced by CD5+CD1dhi regulatory B-cells. Taken together, our data support the conclusion that sustained ERK1/2 activation in B-cells suppresses immune-mediated demyelination via increasing activation of regulatory B10 cells.

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