Search results for: MOG peptide Proteins
#39197551 
2024/08/27
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Inflammation-related abnormal dynamic brain activity correlates with cognitive impairment in first-episode, drug-naïve major depressive disorder.
Cognitive impairment is common in major depressive disorder (MDD) and potentially linked to inflammation-induced alterations in brain function. However, the relationship between inflammation, dynamic brain activity, and cognitive impairment in MDD remains unclear.Yifan Jing, Yuan Liu, Yuwen Zhou, Meijuan Li, Ying Gao, Bin Zhang, Jie Li
1100 related Products with: Inflammation-related abnormal dynamic brain activity correlates with cognitive impairment in first-episode, drug-naïve major depressive disorder.
100 assays16 Arrays/Slide48 assays2 Pieces/Box100 assays8 Sample Kit32-50 Sample Kit
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#39142423 2024/08/13
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Retigabine, a potassium channel opener, restores thalamocortical neuron functionality in a murine model of autoimmune encephalomyelitis.
Multiple Sclerosis (MS) is an autoimmune neurodegenerative disease, whose primary hallmark is the occurrence of inflammatory lesions in white and grey matter structures. Increasing evidence in MS patients and respective murine models reported an impaired ionic homeostasis driven by inflammatory-demyelination, thereby profoundly affecting signal propagation. However, the impact of a focal inflammatory lesion on single-cell and network functionality has hitherto not been fully elucidated.Luca Fazio, Venu Narayanan Naik, Rajeevan Narayanan Therpurakal, Fiorella M Gomez Osorio, Nicole Rychlik, Julia Ladewig, Michael Strüber, Manuela Cerina, Sven G Meuth, Thomas Budde
2467 related Products with: Retigabine, a potassium channel opener, restores thalamocortical neuron functionality in a murine model of autoimmune encephalomyelitis.
100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized1 Product tipe: Instrumen100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized
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#39090252 2024/08/01
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Siponimod treatment response shows partial BDNF dependency in multiple sclerosis models.
So far, only a small number of medications are effective in progressive multiple sclerosis (MS). The sphingosine-1-phosphate-receptor (S1PR)-1,5 modulator siponimod, licensed for progressive MS, is acting both on peripheral immune cells and in the central nervous system (CNS). So far it remains elusive, whether those effects are related to the neurotrophin brain derived neurotrophic factor (BDNF). We hypothesized that BDNF in immune cells might be a prerequisite to reduce disease activity in experimental autoimmune encephalomyelitis (EAE) and prevent neurotoxicity. MOG immunized wild type (WT) and BDNF knock-out (BDNF) mice were treated with siponimod or vehicle and scored daily in a blinded manner. Immune cell phenotyping was performed via flow cytometry. Immune cell infiltration and demyelination of spinal cord were assessed using immunohistochemistry. In vitro, effects on neurotoxicity and mRNA regulation were investigated using dorsal root ganglion cells incubated with EAE splenocyte supernatant. Siponimod led to a dose-dependent reduction of EAE scores in chronic WT EAE. Using a suboptimal dosage of 0.45 µg/day, siponimod reduced clinical signs of EAE independent of BDNF-expression in immune cells in accordance with reduced infiltration and demyelination. Th and Tc cells in secondary lymphoid organs were dose-dependently reduced, paralleled with an increase of regulatory T cells. In vitro, neuronal viability trended towards a deterioration after incubation with EAE supernatant; siponimod showed a slight rescue effect following treatment of WT splenocytes. Neuronal gene expression for CCL2 and CX3CL1 was elevated after incubation with EAE supernatant, which was reversed after siponimod treatment for WT, but not for BNDF. Apoptosis markers and alternative death pathways were not affected. Siponimod exerts both anti-inflammatory and neuroprotective effects, partially related to BDNF-expression. This might in part explain effectiveness during progression in MS and could be a target for therapy.Hasan Hüseyin Hendek, Alina Blusch, Neele Heitmann, Sarah Oberhagemann, Seray Demir, Xiomara Pedreiturria, Ralf Gold, Simon Faissner
1958 related Products with: Siponimod treatment response shows partial BDNF dependency in multiple sclerosis models.
1ml1 Set16 Arrays/Slide
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#39002186 2024/06/20
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Clinical characteristics, immunological alteration and distinction of MOG-IgG-associated disorders and GFAP-IgG-associated disorders.
The classification of autoimmune encephalitis (AE) is based on the presence of different types of antibodies. Currently, the clinical manifestations and treatment regimens of patients with all types of AE exhibit similarities. However, the presence of immunological distinctions among different types of AE remains uncertain. In this study, we prospectively collected clinical data, as well as blood and cerebrospinal fluid (CSF) samples from patients diagnosed with MOG antibody-associated disease (MOGAD) or GFAP astrocytopathy (GFAP-A), in order to assess changes in inflammatory biomarkers such as immunoglobulin oligoclonal bands, cytokines in serum and CSF, as well as peripheral blood lymphocyte subtypes within different subsets. To further distinguish the immune response in patients with MOGAD and GFAP-A from that of healthy individuals, we prospectively recruited 20 hospitalized patients diagnosed with AE. Among them, 15 (75%) tested positive for MOG antibodies, 4 (20%) tested positive for GFAP antibodies, and 1 (5%) tested positive for both MOG and GFAP antibodies. These patients were then followed up for a period of 18 months. Compared to healthy controls (HC), AE patients exhibited elevated levels of MIP-1beta, SDF-1alpha, IL-12p70, IL-5, IL-1RA, IL-8 and decreased levels of IL-23, IL-31, IFN-alpha, IL-7, TNF-beta and TNF-alpha in serum. The CSF of AE patients showed increased levels of IL-1RA, IL-6 and IL-2 while decreased levels of RANTES, IL-18,IL-7,TNF-beta,TNF-alpha,RANTES,Eotaxin,and IL-9. The level of MCP-1 in the CSF of GFAP-A patients was found to be lower compared to that of MOGAD patients, while RANTES levels were higher. And the levels of IL-17A, Eotaxin, GRO-alpha, IL-8, IL-1beta, MIP-1beta were higher in the CSF of patients with epilepsy. The presence of intrathecal immune responses is also observed in patients with spinal muscular atrophy (SMA). However, no biomarker was found to be associated with disease severity in patients with AE. Among the 17 patients, recovery was observed, while 2 patients experienced persistent symptoms after an 18-month follow-up period. Additionally, within one year of onset, 8 patients had a single recurrence. Therefore, the immunological profiles of MOGAD and GFAP-A patients differ from those of normal individuals, and the alterations in cytokine levels may also exhibit a causal association with the clinical presentations, such as seizure.Rongrong Zeng, Lu He, Zhuo Kuang, Yiemin Jian, Meijuan Qiu, Yuting Liu, Mengdie Hu, Yizhi Ye, Liwen Wu
1627 related Products with: Clinical characteristics, immunological alteration and distinction of MOG-IgG-associated disorders and GFAP-IgG-associated disorders.
1,000 tests100ul1000 TESTS/0.65ml1 mg1000 100ug100 mg1000 tests100ug500 MG100ul
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#38985855 2024/07/10
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Preclinical studies show that Co-STARs combine the advantages of chimeric antigen and T cell receptors for the treatment of tumors with low antigen densities.
Two types of engineered T cells have been successfully used to treat patients with cancer, one with an antigen recognition domain derived from antibodies [chimeric antigen receptors (CARs)] and the other derived from T cell receptors (TCRs). CARs use high-affinity antigen-binding domains and costimulatory domains to induce T cell activation but can only react against target cells with relatively high amounts of antigen. TCRs have a much lower affinity for their antigens but can react against target cells displaying only a few antigen molecules. Here, we describe a new type of receptor, called a Co-STAR (for costimulatory synthetic TCR and antigen receptor), that combines aspects of both CARs and TCRs. In Co-STARs, the antigen-recognizing components of TCRs are replaced by high-affinity antibody fragments, and costimulation is provided by two modules that drive NF-κB signaling (MyD88 and CD40). Using a TCR-mimic antibody fragment that targets a recurrent p53 neoantigen presented in a common human leukocyte antigen (HLA) allele, we demonstrate that T cells equipped with Co-STARs can kill cancer cells bearing low densities of antigen better than T cells engineered with conventional CARs and patient-derived TCRs in vitro. In mouse models, we show that Co-STARs mediate more robust T cell expansion and more durable tumor regressions than TCRs similarly modified with MyD88 and CD40 costimulation. Our data suggest that Co-STARs may have utility for other peptide-HLA antigens in cancer and other targets where antigen density may limit the efficacy of engineered T cells.Brian J Mog, Nikita Marcou, Sarah R DiNapoli, Alexander H Pearlman, Tushar D Nichakawade, Michael S Hwang, Jacqueline Douglass, Emily Han-Chung Hsiue, Stephanie Glavaris, Katharine M Wright, Maximilian F Konig, Suman Paul, Nicolas Wyhs, Jiaxin Ge, Michelle S Miller, P Azurmendi, Evangeline Watson, Drew M Pardoll, Sandra B Gabelli, Chetan Bettegowda, Nickolas Papadopoulos, Kenneth W Kinzler, Bert Vogelstein, Shibin Zhou
1186 related Products with: Preclinical studies show that Co-STARs combine the advantages of chimeric antigen and T cell receptors for the treatment of tumors with low antigen densities.
0.1ml (1mg/ml)100 ug/vial0.1ml (1mg/ml)1 mg0.1ml (1mg/ml)0.1ml (1mg/ml)0.1ml (1mg/ml)0.2 mg50ul 100 G50ul (1mg/ml)
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#38928437 2024/06/19
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IL-6 Inhibition as a Therapeutic Target in Aged Experimental Autoimmune Encephalomyelitis.
Multiple sclerosis (MS) onset at an advanced age is associated with a higher risk of developing progressive forms and a greater accumulation of disability for which there are currently no effective disease-modifying treatments. Immunosenescence is associated with the production of the senescence-associated secretory phenotype (SASP), with IL-6 being one of the most prominent cytokines. IL-6 is a determinant for the development of autoimmunity and neuroinflammation and is involved in the pathogenesis of MS. Herein, we aimed to preclinically test the therapeutic inhibition of IL-6 signaling in experimental autoimmune encephalomyelitis (EAE) as a potential age-specific treatment for elderly MS patients. Young and aged mice were immunized with myelin oligodendrocyte protein (MOG) and examined daily for neurological signs. Mice were randomized and treated with anti-IL-6 antibody. Inflammatory infiltration was evaluated in the spinal cord and the peripheral immune response was studied. The blockade of IL-6 signaling did not improve the clinical course of EAE in an aging context. However, IL-6 inhibition was associated with an increase in the peripheral immunosuppressive response as follows: a higher frequency of CD4 T cells producing IL-10, and increased frequency of inhibitory immune check points PD-1 and Tim-3 on CD4 T cells and Lag-3 and Tim-3 on CD8 T cells. Our results open the window to further studies aimed to adjust the anti-IL-6 treatment conditions to tailor an effective age-specific therapy for elderly MS patients.María Dema, Herena Eixarch, Mireia Castillo, Xavier Montalban, Carmen Espejo
1370 related Products with: IL-6 Inhibition as a Therapeutic Target in Aged Experimental Autoimmune Encephalomyelitis.
48 assays 96 assays 0.1ml (1mg/ml)48 assays 96 assays 0.1ml (1mg/ml)48 assays48 samples48 assays 96 assays
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#38926356 2024/06/26
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Myelin-reactive B cells exacerbate CD4 T cell-driven CNS autoimmunity in an IL-23-dependent manner.
B cells and T cells collaborate in multiple sclerosis (MS) pathogenesis. IgH mice possess a B cell repertoire skewed to recognize myelin oligodendrocyte glycoprotein (MOG). Here, we show that upon immunization with the T cell-obligate autoantigen, MOG, IgH mice develop rapid and exacerbated experimental autoimmune encephalomyelitis (EAE) relative to wildtype (WT) counterparts, characterized by aggregation of T and B cells in the IgH meninges and by CD4 T helper 17 (Th17) cells in the CNS. Production of the Th17 maintenance factor IL-23 is observed from IgH CNS-infiltrating and meningeal B cells, and in vivo blockade of IL-23p19 attenuates disease severity in IgH mice. In the CNS parenchyma and dura mater of IgH mice, we observe an increased frequency of CD4PD-1CXCR5 T cells that share numerous characteristics with the recently described T peripheral helper (Tph) cell subset. Further, CNS-infiltrating B and Tph cells from IgH mice show increased reactive oxygen species (ROS) production. Meningeal inflammation, Tph-like cell accumulation in the CNS and B/Tph cell production of ROS were all reduced upon p19 blockade. Altogether, MOG-specific B cells promote autoimmune inflammation of the CNS parenchyma and meninges in an IL-23-dependent manner.Mohamed Reda Fazazi, Prenitha Mercy Ignatius Arokia Doss, Resel Pereira, Neva Fudge, Aryan Regmi, Charles Joly-Beauparlant, Irshad Akbar, Asmita Pradeep Yeola, Benoit Mailhot, Joanie Baillargeon, Philippe Grenier, Nicolas Bertrand, Steve Lacroix, Arnaud Droit, Craig S Moore, Olga L Rojas, Manu Rangachari
2729 related Products with: Myelin-reactive B cells exacerbate CD4 T cell-driven CNS autoimmunity in an IL-23-dependent manner.
100ug
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#38892275 2024/05/31
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Myelin Oligodendrocyte Glycoprotein (MOG)35-55 Mannan Conjugate Induces Human T-Cell Tolerance and Can Be Used as a Personalized Therapy for Multiple Sclerosis.
We have previously performed preclinical studies with the oxidized mannan-conjugated peptide MOG35-55 (OM-MOG35-55) in vivo (EAE mouse model) and in vitro (human peripheral blood) and demonstrated that OM-MOG35-55 suppresses antigen-specific T cell responses associated with autoimmune demyelination. Based on these results, we developed different types of dendritic cells (DCs) from the peripheral blood monocytes of patients with multiple sclerosis (MS) or healthy controls presenting OM-MOG35-55 or MOG-35-55 to autologous T cells to investigate the tolerogenic potential of OM-MOG35-55 for its possible use in MS therapy. To this end, monocytes were differentiated into different DC types in the presence of IL-4+GM-CSF ± dexamethasone (DEXA) ± vitamin D3 (VITD3). At the end of their differentiation, the DCs were loaded with peptides and co-cultured with T cells +IL-2 for 4 antigen presentation cycles. The phenotypes of the DC and T cell populations were analyzed using flow cytometry and the secreted cytokines using flow cytometry or ELISA. On day 8, the monocytes had converted into DCs expressing the typical markers of mature or immature phenotypes. Co-culture of T cells with all DC types for 4 antigen presentation cycles resulted in an increase in memory CD4+ T cells compared to memory CD8+ T cells and a suppressive shift in secreted cytokines, mainly due to increased TGF-β1 levels. The best tolerogenic effect was obtained when patient CD4+ T cells were co-cultured with VITD3-DCs presenting OM-MOG35-55, resulting in the highest levels of CD4+PD-1+ T cells and CD4+CD25+Foxp3+ Τ cells. In conclusion, the tolerance induction protocols presented in this work demonstrate that OM-MOG35-55 could form the basis for the development of personalized therapeutic vaccines or immunomodulatory treatments for MS.Maria Rodi, Anne-Lise de Lastic, Ioannis Panagoulias, Ioanna Aggeletopoulou, Kostas Kelaidonis, John Matsoukas, Vasso Apostolopoulos, Athanasia Mouzaki
1828 related Products with: Myelin Oligodendrocyte Glycoprotein (MOG)35-55 Mannan Conjugate Induces Human T-Cell Tolerance and Can Be Used as a Personalized Therapy for Multiple Sclerosis.
100ug100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug100ug Lyophilized100ug Lyophilized100ug100ug Lyophilized
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#38844244 2024/06/04
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Fluorinated apelin-13 mediates neuroprotective effects in multiple sclerosis models.
Multiple sclerosis (MS) is an autoimmune and neurodegenerative disease leading to demyelination and axonal loss. Current treatments are immunomodulatory or immunosuppressive drugs acting on the inflammatory component. However, these treatments do not adequately address the crucial aspect of neuroprotection. Recently, an association between an altered balance of adipokines and MS has been proposed as both a risk factor for developing MS and a chronic disease aggravating factor. Specifically, a decrease of apelin plasma levels in MS patients compared to controls correlates with the number of relapses and disease severity. Here we report a dramatic downregulation of apelin levels in the CNS of EAE mice which is also detected in MS patients brain samples compared to controls. Exploiting innovative design and synthesis techniques, we engineered a novel fluorinated apelin-13 peptide characterized by enhanced plasmatic stability compared to its native counterpart. With this peptide, we assessed the potential therapeutic benefits of apelin preventive supplementation in the EAE mouse model. We show that the fluorinated Apelin-13 peptide ameliorates EAE clinical score and preserves myelin content in the EAE MOG model recapitulating the progressive form of disease. These results combined with ex-vivo experiments in brain organotypic slices and in vitro studies in neurons and primary microglia and macrophages suggest that apelin has neuroprotective effects and influences the microglia/macrophages function.Dafni Birmpili, Imane Charmarké-Askar, Caroline Spenlé, Stéphanie Riché, Lucas Dinh Pham-Van, Thomas Kuntzel, Thanos Xhurxhi, Aurélien Riou, Dominique Bonnet, Dominique Bagnard
2815 related Products with: Fluorinated apelin-13 mediates neuroprotective effects in multiple sclerosis models.
16 Arrays/Slide5 g5mg16 Arrays/Slide
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#38822334 2024/05/31
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Therapeutic role of interferon-γ in experimental autoimmune encephalomyelitis is mediated through a tolerogenic subset of splenic CD11b myeloid cells.
Cumulative evidence has established that Interferon (IFN)-γ has both pathogenic and protective roles in Multiple Sclerosis and the animal model, Experimental Autoimmune Encephalomyelitis (EAE). However, the underlying mechanisms to the beneficial effects of IFN-γ are not well understood. In this study, we found that IFN-γ exerts therapeutic effects on chronic, relapsing-remitting, and chronic progressive EAE models. The frequency of regulatory T (Treg) cells in spinal cords from chronic EAE mice treated with IFN-γ was significantly increased with no effect on Th1 and Th17 cells. Consistently, depletion of FOXP3-expressing cells blocked the protective effects of IFN-γ, indicating that the therapeutic effect of IFN-γ depends on the presence of Treg cells. However, IFN-γ did not trigger direct in vitro differentiation of Treg cells. In vivo administration of blocking antibodies against either interleukin (IL)-10, transforming growth factor (TGF)-β or program death (PD)-1, revealed that the protective effects of IFN-γ in EAE were also dependent on TGF-β and PD-1, but not on IL-10, suggesting that IFN-γ might have an indirect role on Treg cells acting through antigen-presenting cells. Indeed, IFN-γ treatment increased the frequency of a subset of splenic CD11b myeloid cells expressing TGF-β-Latency Associated Peptide (LAP) and program death ligand 1 (PD-L1) in a signal transducer and activator of transcription (STAT)-1-dependent manner. Furthermore, splenic CD11b cells from EAE mice preconditioned in vitro with IFN-γ and myelin oligodendrocyte glycoprotein (MOG) peptide exhibited a tolerogenic phenotype with the capability to induce conversion of naïve CD4 T cells mediated by secretion of TGF-β. Remarkably, adoptive transfer of splenic CD11b cells from IFN-γ-treated EAE mice into untreated recipient mice ameliorated clinical symptoms of EAE and limited central nervous system infiltration of mononuclear cells and effector helper T cells. These results reveal a novel cellular and molecular mechanism whereby IFN-γ promotes beneficial effects in EAE by endowing splenic CD11b myeloid cells with tolerogenic and therapeutic activities.Gabriel Arellano, Eric Acuña, Eileah Loda, Lindsay Moore, Juan E Tichauer, Cristian Castillo, Fabian Vergara, Paula I Burgos, Pablo Penaloza-MacMaster, Stephen D Miller, Rodrigo Naves