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  1. Article ; Online: Inverse association between age and inflammatory disease activity in multiple sclerosis.

    Segal, Benjamin M

    Nature reviews. Neurology

    2023  Volume 19, Issue 10, Page(s) 577–578

    MeSH term(s) Humans ; Multiple Sclerosis/complications ; Multiple Sclerosis, Relapsing-Remitting
    Language English
    Publishing date 2023-08-10
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 2491514-2
    ISSN 1759-4766 ; 1759-4758
    ISSN (online) 1759-4766
    ISSN 1759-4758
    DOI 10.1038/s41582-023-00844-9
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 6257: Show issues Location:
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  2. Article: The Diversity of Encephalitogenic CD4+ T Cells in Multiple Sclerosis and Its Animal Models.

    Segal, Benjamin M

    Journal of clinical medicine

    2019  Volume 8, Issue 1

    Abstract: Autoreactive CD4+ T cells, which target antigens in central nervous system (CNS) myelin, are widely believed to play a critical role in the pathogenesis of multiple sclerosis (MS) in concert with other immune effectors. This theory is supported by data ... ...

    Abstract Autoreactive CD4+ T cells, which target antigens in central nervous system (CNS) myelin, are widely believed to play a critical role in the pathogenesis of multiple sclerosis (MS) in concert with other immune effectors. This theory is supported by data from animal model experiments, genome-wide association studies, and immune profiles of individuals with MS. Furthermore, disease modifying agents that target lymphocytes significantly reduce the rate of MS clinical exacerbations. However, the properties of myelin-reactive CD4+ T cells that are critical for their pathogenic activities are not understood completely. This article reviews the literature on encephalitogenic CD4+ T cells, with an emphasis on T-helper (Th) lineage and cytokine production. An increased understanding of the spectrum of encephalitogenic T cells and how they differ from protective subsets is necessary for the development of the next generation of more effective and safer immunomodulatory therapies customized for individuals with MS and related disorders.
    Language English
    Publishing date 2019-01-19
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2662592-1
    ISSN 2077-0383
    ISSN 2077-0383
    DOI 10.3390/jcm8010120
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  3. Article ; Online: Enhancing natural killer cells is beneficial in multiple sclerosis - Commentary.

    Segal, Benjamin M

    Multiple sclerosis (Houndmills, Basingstoke, England)

    2018  Volume 25, Issue 4, Page(s) 513–514

    MeSH term(s) Humans ; Killer Cells, Natural ; Multiple Sclerosis
    Language English
    Publishing date 2018-11-13
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Comment
    ZDB-ID 1290669-4
    ISSN 1477-0970 ; 1352-4585
    ISSN (online) 1477-0970
    ISSN 1352-4585
    DOI 10.1177/1352458518809296
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  4. Article ; Online: Modulation of the Innate Immune System: A Future Approach to the Treatment of Neurological Disease.

    Segal, Benjamin M

    Clinical immunology (Orlando, Fla.)

    2018  Volume 189, Page(s) 1–3

    MeSH term(s) Animals ; Humans ; Immune System/immunology ; Immunity, Innate/immunology ; Nervous System Diseases/immunology ; Nervous System Diseases/therapy ; Translational Medical Research
    Language English
    Publishing date 2018-03-28
    Publishing country United States
    Document type Editorial ; Introductory Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1459903-x
    ISSN 1521-7035 ; 1521-6616
    ISSN (online) 1521-7035
    ISSN 1521-6616
    DOI 10.1016/j.clim.2018.03.003
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  5. Article ; Online: The 2020 FASEB Science Research Conference on Translational Neuroimmunology: From Mechanisms to Therapeutics, June 29-30, 2020.

    Lane, Thomas E / Segal, Benjamin M

    FASEB journal : official publication of the Federation of American Societies for Experimental Biology

    2020  Volume 34, Issue 11, Page(s) 14064–14068

    MeSH term(s) Autoimmune Diseases of the Nervous System/pathology ; Autoimmune Diseases of the Nervous System/therapy ; Congresses as Topic ; Humans ; Neuroimmunomodulation ; Societies, Medical/trends ; Translational Medical Research/trends
    Keywords covid19
    Language English
    Publishing date 2020-10-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 639186-2
    ISSN 1530-6860 ; 0892-6638
    ISSN (online) 1530-6860
    ISSN 0892-6638
    DOI 10.1096/fj.202002065
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  6. Article ; Online: The Diversity of Encephalitogenic CD4+ T Cells in Multiple Sclerosis and Its Animal Models

    Benjamin M. Segal

    Journal of Clinical Medicine, Vol 8, Iss 1, p

    2019  Volume 120

    Abstract: Autoreactive CD4+ T cells, which target antigens in central nervous system (CNS) myelin, are widely believed to play a critical role in the pathogenesis of multiple sclerosis (MS) in concert with other immune effectors. This theory is supported by data ... ...

    Abstract Autoreactive CD4+ T cells, which target antigens in central nervous system (CNS) myelin, are widely believed to play a critical role in the pathogenesis of multiple sclerosis (MS) in concert with other immune effectors. This theory is supported by data from animal model experiments, genome-wide association studies, and immune profiles of individuals with MS. Furthermore, disease modifying agents that target lymphocytes significantly reduce the rate of MS clinical exacerbations. However, the properties of myelin-reactive CD4+ T cells that are critical for their pathogenic activities are not understood completely. This article reviews the literature on encephalitogenic CD4+ T cells, with an emphasis on T-helper (Th) lineage and cytokine production. An increased understanding of the spectrum of encephalitogenic T cells and how they differ from protective subsets is necessary for the development of the next generation of more effective and safer immunomodulatory therapies customized for individuals with MS and related disorders.
    Keywords Multiple Sclerosis ; experimental autoimmune encephalomyelitis ; T-helper cells ; cytokines ; Medicine ; R
    Subject code 570
    Language English
    Publishing date 2019-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Respiratory tract Moraxella catarrhalis and Klebsiella pneumoniae can promote pathogenicity of myelin-reactive Th17 cells.

    Mannion, Jenny M / Segal, Benjamin M / McLoughlin, Rachel M / Lalor, Stephen J

    Mucosal immunology

    2023  Volume 16, Issue 4, Page(s) 399–407

    Abstract: The respiratory tract is home to a diverse microbial community whose influence on local and systemic immune responses is only beginning to be appreciated. The airways have been linked with the trafficking of myelin-specific T-cells in the preclinical ... ...

    Abstract The respiratory tract is home to a diverse microbial community whose influence on local and systemic immune responses is only beginning to be appreciated. The airways have been linked with the trafficking of myelin-specific T-cells in the preclinical stages of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Th17 cells are important pathogenic effectors in MS and EAE but are innocuous immediately following differentiation. Upregulation of the cytokine GM-CSF appears to be a critical step in their acquisition of pathogenic potential, but little is known about the mechanisms that mediate this process. Here, primed myelin-specific Th17 cells were transferred to congenic recipient mice prior to exposure to various human respiratory tract-associated bacteria and T-cell trafficking, phenotype and the severity of resulting EAE were monitored. Disease was exacerbated in mice exposed to the Proteobacteria Moraxella catarrhalis and Klebsiella pneumoniae, but not the Firmicute Veillonella parvula, and this was associated with significantly increased GM-CSF
    MeSH term(s) Mice ; Humans ; Animals ; Granulocyte-Macrophage Colony-Stimulating Factor ; Moraxella catarrhalis ; Klebsiella pneumoniae ; Myelin Sheath/pathology ; Th17 Cells ; Virulence ; Encephalomyelitis, Autoimmune, Experimental/pathology ; Multiple Sclerosis/pathology ; Respiratory System ; Mice, Inbred C57BL ; Th1 Cells
    Chemical Substances Granulocyte-Macrophage Colony-Stimulating Factor (83869-56-1)
    Language English
    Publishing date 2023-04-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2411370-0
    ISSN 1935-3456 ; 1933-0219
    ISSN (online) 1935-3456
    ISSN 1933-0219
    DOI 10.1016/j.mucimm.2023.04.003
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    Zs.A 6796: Show issues Location:
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  8. Article ; Online: Biological aging in multiple sclerosis.

    Zhang, Yinan / Atkinson, Jeffrey / Burd, Christin E / Graves, Jennifer / Segal, Benjamin M

    Multiple sclerosis (Houndmills, Basingstoke, England)

    2023  Volume 29, Issue 14, Page(s) 1701–1708

    Abstract: Multiple sclerosis (MS) is most likely to adopt a progressive clinical course during middle age or beyond, and the number of older adults with MS is steadily increasing. Developing new strategies to manage progressive forms of MS, which do not respond to ...

    Abstract Multiple sclerosis (MS) is most likely to adopt a progressive clinical course during middle age or beyond, and the number of older adults with MS is steadily increasing. Developing new strategies to manage progressive forms of MS, which do not respond to currently available disease-modifying therapies (DMTs), will require a deeper understanding of the mechanisms by which biological aging interacts with pathogenic pathways to propel disability accumulation. In experimental autoimmune encephalomyelitis (EAE), a widely used preclinical mouse model of MS, middle-aged animals experience a more severe and protracted clinical course than their younger counterparts. This exacerbated disease course is accompanied by persistent neuroinflammation. Clinical studies of age-related biomarkers, such as telomere length, senescence markers, and DNA methylation, suggest that biological aging is accelerated in people with MS compared with age- and sex-matched healthy controls. Furthermore, distinguishing biological age from chronological may afford more precision in determining aging effects in MS. Here we review the current literature on aging biology and its impact on MS pathogenesis. Future research on this topic may lead to the development of novel biomarkers and senotherapy agents that slow neurological decline in people with progressive MS by targeting relevant aging-related pathways.
    MeSH term(s) Middle Aged ; Humans ; Mice ; Animals ; Aged ; Multiple Sclerosis/drug therapy ; Multiple Sclerosis, Chronic Progressive/drug therapy ; Encephalomyelitis, Autoimmune, Experimental ; Aging ; Disease Progression ; Biomarkers
    Chemical Substances Biomarkers
    Language English
    Publishing date 2023-10-25
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1290669-4
    ISSN 1477-0970 ; 1352-4585
    ISSN (online) 1477-0970
    ISSN 1352-4585
    DOI 10.1177/13524585231204122
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    Zs.A 4428: Show issues Location:
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  9. Article ; Online: Treatment of neuromyelitis optica spectrum disorders.

    Romeo, Andrew R / Segal, Benjamin M

    Current opinion in rheumatology

    2019  Volume 31, Issue 3, Page(s) 250–255

    Abstract: Purpose of review: This review discusses concepts for diagnosing neuromyelitis optica spectrum disorders (NMOSD), distinguishing NMOSD from other inflammatory diseases of the central nervous system, and highlights recent and forthcoming data on acute ... ...

    Abstract Purpose of review: This review discusses concepts for diagnosing neuromyelitis optica spectrum disorders (NMOSD), distinguishing NMOSD from other inflammatory diseases of the central nervous system, and highlights recent and forthcoming data on acute and maintenance therapy of NMOSD.
    Recent findings: The neurologic manifestations of NMOSD are heterogenous, extending beyond classic presentations of optic neuritis and longitudinally extensive transverse myelitis. NMOSD may be comorbid with rheumatologic diseases, such as systemic lupus erythematosus, but is recognized as a distinct entity. Recent studies of acute treatment of NMOSD support early use of plasmapheresis. Relapse prevention is essential, as relapses can be disabling and patients may have only partial recovery. Current practice generally recommends at least 5 years of maintenance treatment. Recent randomized data demonstrates superiority of rituximab over azathioprine. Phase 3 trials have recently been completed or are underway studying novel therapies employing B-cell depletion, complement inhibition, and cell-based mechanisms (among other mechanisms) for maintenance therapy of NMOSD.
    Summary: NMOSD is a heterogeneous but well-defined clinical entity, distinct from other neurologic and systemic inflammatory diseases, and treatment is poised for expansion.
    MeSH term(s) Azathioprine/therapeutic use ; Comorbidity ; Diagnosis, Differential ; Humans ; Immunosuppressive Agents/therapeutic use ; Lymphocyte Depletion ; Neuromyelitis Optica/diagnosis ; Neuromyelitis Optica/drug therapy ; Neuromyelitis Optica/therapy ; Plasmapheresis ; Recurrence ; Rituximab/therapeutic use
    Chemical Substances Immunosuppressive Agents ; Rituximab (4F4X42SYQ6) ; Azathioprine (MRK240IY2L)
    Language English
    Publishing date 2019-03-28
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1045317-9
    ISSN 1531-6963 ; 1040-8711
    ISSN (online) 1531-6963
    ISSN 1040-8711
    DOI 10.1097/BOR.0000000000000603
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  10. Article ; Online: TAM receptor signaling dictates lesion location and clinical phenotype during experimental autoimmune encephalomyelitis.

    Gardner, Ashley Munie / Atkinson, Jeffrey R / Wilkinson, Nicole M / Jerome, Andrew D / Bellinger, Calli E / Sas, Andrew R / Segal, Benjamin M

    Journal of neuroimmunology

    2023  Volume 375, Page(s) 578016

    Abstract: Experimental autoimmune encephalomyelitis (EAE), induced by the adoptive transfer of Th17 cells, typically presents with ascending paralysis and inflammatory demyelination of the spinal cord. Brain white matter is relatively spared. Here we show that ... ...

    Abstract Experimental autoimmune encephalomyelitis (EAE), induced by the adoptive transfer of Th17 cells, typically presents with ascending paralysis and inflammatory demyelination of the spinal cord. Brain white matter is relatively spared. Here we show that treatment of Th17 transfer recipients with a highly selective inhibitor to the TAM family of tyrosine kinase receptors results in ataxia associated with a shift of the inflammatory infiltrate to the hindbrain parenchyma. During homeostasis and preclinical EAE, hindbrain microglia express high levels of the TAM receptor Mer. Our data suggest that constitutive TAM receptor signaling in hindbrain microglia confers region-specific protection against Th17 mediated EAE.
    MeSH term(s) Animals ; Mice ; Encephalomyelitis, Autoimmune, Experimental ; Spinal Cord/pathology ; Microglia/pathology ; Receptor Protein-Tyrosine Kinases ; Mice, Inbred C57BL
    Chemical Substances Receptor Protein-Tyrosine Kinases (EC 2.7.10.1)
    Language English
    Publishing date 2023-01-20
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 8335-5
    ISSN 1872-8421 ; 0165-5728
    ISSN (online) 1872-8421
    ISSN 0165-5728
    DOI 10.1016/j.jneuroim.2023.578016
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