Antibody response in MOG35–55 induced EAE

Lalive, Patrice H.; Molnarfi, Nicolas; Benkhoucha, Mahdia; Weber, Martin; Santiago-Raber, Marie-Laure

doi:10.1016/j.jneuroim.2011.09.005

Cited by 32 publications

(32 citation statements)

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“…In addition, we recently demonstrated both the activation of B cells and the generation of specific antibodies against RNA in the MOG -EAE model [19]. Of interest, we also show in this present work that TLR7-deficient mice produce less circulating autoantibodies against RNA and RNA-related antigens such as small nuclear ribonucleoproteins (snRNPs).…”

Section: Introductionsupporting

confidence: 71%

“…These observations have been attributed to the loss of IL-10-secreting suppressive B cells in the first case and to diminished B-cell support of CD4 + T cells in the latter case [45]. Recently, we demonstrated that direct immunization with MOG 35-55 triggers autoreactive B-cell activation, as exemplified by increased expression levels of CD69 and MHC II molecules by B cells, together with an elevated frequency of B cells within the GCs of secondary lymphoid organs and within the CNS [19]. Thus, reductions in pDC and B-cell frequencies in TLR7-deficient mice may contribute to the protective effect.…”

Section: Discussionmentioning

confidence: 95%

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TLR7 signaling exacerbates CNS autoimmunity through downregulation of Foxp3⁺Treg cells

et al. 2013

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The innate Toll-like receptor 7 (TLR7) detects infections by recognizing viral and bacterial single-stranded RNA. In addition to pathogen-derived RNA, immune cells expressing high levels of TLR7, such as B cells and dendritic cells (DCs), can be activated by self-RNA. During myelin-induced experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, TLR7 expression is increased within the central nervous system (CNS). To define the contribution of TLR7 to the development of EAE, we evaluated the course of the disease in C57BL/6-Tlr7-deficient mice compared with that in WT mice and found that TLR7-deficient mice had decreased disease severity. This protection was associated with decreased myelin oligodendrocyte glycoprotein-specific T-cell activation by primed DCs, decreased circulating autoantibodies, attenuated inflammation within the CNS, and increased Foxp3 + regulatory T cells in the periphery and in the CNS. In conclusion, we show that TLR7 is involved in the maintenance of autoimmunity in the pathogenesis of EAE.Keywords: EAE r IL-10 r Multiple sclerosis r TLR7 r Treg cell IntroductionRecognition of microbial components by Toll-like receptors (TLRs) is crucial for host responses against pathogens. While most TLRs are expressed on the cell surface, others such as TLR3, -7, -8, and -9 are expressed intracellularly within endosomal compartments where they detect nucleic acids. Endosomal TLRs recognize viral double-stranded RNA (TLR3), unmethylated CpG DNA Correspondence: Dr. Marie-Laure Santiago-Raber e-mail: marie.santiago@unige.ch (TLR9), and viral single-stranded RNA or synthetic compounds such as imidazoquinolines (TLR7/TLR8) (as reviewed by Kawai and Akira [1]). Previous studies have further provided evidence for the involvement of TLR signaling in the induction of autoantibodies [2,3]. Others studies have implicated TLR7 gene duplication in the pathogenesis of autoimmune diseases such as lupus [4,5]. TLR7 is mainly expressed by B cells but also by dendritic cells (DCs), principally plasmacytoid DCs (pDCs). B cells and pDCs appear to have developed specialized mechanisms for enhancing the delivery of potential ligands to TLR7-and TLR9-containing compartments [6]. In view of the pivotal role of (i) DCs in regulating immunity and tolerance [7], (ii) B cells in the C 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2014. 44: 46-57 Cellular immune response 47 adaptive immune response, and (iii) regulatory T (Treg) cells in maintaining T-cell tolerance, we evaluated the importance of DC, B-cell, and Treg-cell activation and generation by ligandbound TLR7 in the framework of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). MS is an immune-mediated disease of the central nervous system (CNS), characterized by the infiltration of inflammatory cells, including autoreactive CD4 + T cells and antigen-presenting cells (APCs), which leads to demyelination and axonal damage [8]. Even though CD4 + T-cell autorea...

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Section: Introductionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 95%

TLR7 signaling exacerbates CNS autoimmunity through downregulation of Foxp3⁺Treg cells

et al. 2013

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“…Its association with other autoimmune conditions (MG, SLE, ADEM, and pediatric MS) is known for years. Recent studies illustrated that autoimmune response to MOG can induce a NMO-like disease in experimental animal models [5].…”

Section: Discussionmentioning

confidence: 99%

Myelin Oligodendrocyte Glycoprotein (MOG) Associated Neuromyelitis Optica (NMO) Presenting with Isolated Absent F Wave

Nahrir¹,

Kajtazi²,

Saeedi³

2016

J Neurol Neurosurg

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We describe an unusual presentation of Neuromyelitis Optica (NMO). A young boy presented with two days history of acute onset flaccid paraplegia. Electrophysiological study showed only absence of F wave. Initial exam was suggestive of Gullian-Barre Syndrome (GBS). Nevertheless, MRI spine demonstrated a contrast enhancing lesion in conus medullaris. Few days later, patient developed bilateral optic neuritis. NMO was diagnosed then. Antibody to Aquaporin 4 was not found in the serum, but to Myelin Oligodendrocyte Glycoprotein (MOG) was present. Patient was refractory to IV IgG therapy. He continued to develop symptomatic new lesions in brain and spine. Later Rituximab therapy initiation ceased the disease. However, absent "F wave" in Nerve Conduction is quite a perplexing association. It may reflect concurrent peripheral nerve involvement which needs to be explored. This case is unique due to its atypical presentation and also to the best of our knowledge this is the first reported case of MOG positive NMO from Saudi Arabia.

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“…remyelination/axon protection) [15] indicating that the detection of antibodies may be useful in assessing the clinical course of the disease. Even though the presence of the antibody response within the CNS in MS patients is well established, the pathogenic role of antibodies still remains obscure and their antigenic targets have yet to be determined [16,17].…”

Section: Introductionmentioning

confidence: 99%

Pertussis vaccine-induced experimental autoimmune encephalomyelitis in mice

Stojkovic

Maslovarić

Kosanovic

et al. 2014

Translational Neuroscience

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Background: A small dose of the Bordetella pertussis vaccine is used as an adjuvant for the induction of experimental autoimmune encephalomyelitis (EAE) in mice. The effects of two doses of the Pertussis vaccine on clinical signs, antibody titers, and the expression of CD4 and MHC molecules in brain tissue sections of mice with EAE were examined. Methodology: EAE was induced by spinal cord homogenate in Complete Freund adjuvant (CFA) in 30 of 40 C57BL/6 mice divided in groups: EAE mice with a small adjuvant dose of the Pertussis vaccine (EAE-1), EAE mice with a human dose of the Pertussis vaccine (EAE-2), EAE mice (EAE-3). Results: None of the mice from the EAE groups progressed to severe EAE. Five mice from the EAE-2 group were found dead on the 13th day post-immunization. A significant increase of anti-MOG (myelin oligodendrocyte glycoprotein) antibodies was detected in mice with EAE compared to non-treated mice. Myelin loss and brain tissue lesions were observed in EAE-1 and EAE-2 mice compared to EAE-3 and non-treated mice. A high expression of MHC-II and a mild expression of MHC-I was detected in the brains of mice with EAE. No expressions were detected in intact brains. Scattered CD4-positive cells were detected in the brains of EAE-1 and EAE-2 mice compared to EAE-3 and non-treated mice. Conclusion: A small dose of the Bordetella pertussis vaccine could maintain the developed clinical signs and histological changes in mice with EAE, while higher doses led to additional adverse effects. The expression of CD4 and MHC class I and II molecules, as well as an increase in anti-MOG antibodies could be used as markers capable of monitoring the development and progression of EAE.

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Antibody response in MOG35–55 induced EAE

Cited by 32 publications

References 35 publications

TLR7 signaling exacerbates CNS autoimmunity through downregulation of Foxp3⁺Treg cells

TLR7 signaling exacerbates CNS autoimmunity through downregulation of Foxp3⁺Treg cells

Myelin Oligodendrocyte Glycoprotein (MOG) Associated Neuromyelitis Optica (NMO) Presenting with Isolated Absent F Wave

Pertussis vaccine-induced experimental autoimmune encephalomyelitis in mice

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Antibody response in MOG35–55 induced EAE

Cited by 32 publications

References 35 publications

TLR7 signaling exacerbates CNS autoimmunity through downregulation of Foxp3+Treg cells

TLR7 signaling exacerbates CNS autoimmunity through downregulation of Foxp3+Treg cells

Myelin Oligodendrocyte Glycoprotein (MOG) Associated Neuromyelitis Optica (NMO) Presenting with Isolated Absent F Wave

Pertussis vaccine-induced experimental autoimmune encephalomyelitis in mice

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TLR7 signaling exacerbates CNS autoimmunity through downregulation of Foxp3⁺Treg cells

TLR7 signaling exacerbates CNS autoimmunity through downregulation of Foxp3⁺Treg cells