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  1. Article ; Online: JAK inhibitors differentially modulate B cell activation, maturation and function: A comparative analysis of five JAK inhibitors in an

    Frede, Natalie / Lorenzetti, Raquel / Hüppe, Janika M / Janowska, Iga / Troilo, Arianna / Schleyer, Marei-Theresa / Venhoff, Ana C / Voll, Reinhard E / Thiel, Jens / Venhoff, Nils / Rizzi, Marta

    Frontiers in immunology

    2023  Volume 14, Page(s) 1087986

    Abstract: Background: Janus kinase (JAK) inhibitors have been approved for the treatment of several immune-mediated diseases (IMIDs) including rheumatoid arthritis (RA) and psoriatic arthritis and are in clinical trials for numerous other IMIDs. However, detailed ...

    Abstract Background: Janus kinase (JAK) inhibitors have been approved for the treatment of several immune-mediated diseases (IMIDs) including rheumatoid arthritis (RA) and psoriatic arthritis and are in clinical trials for numerous other IMIDs. However, detailed studies investigating the effects of different JAK inhibitors on B cells are missing. Within this study, we therefore aimed to characterize the effect of JAK inhibition on the B cell compartment.
    Methods: To this end, we investigated the B cell compartment under JAK inhibition and compared the specific effects of the different JAK inhibitors tofacitinib (pan-JAK), baricitinib (JAK1/2), ruxolitinib (JAK1/2), upadacitinib (JAK1/2) as well as filgotinib (selective JAK1) on
    Results: While B cell phenotyping of RA patients showed an increase in marginal zone (MZ) B cells under JAK inhibition, comparison with healthy donors revealed that the relative frequency of MZ B cells was still lower compared to healthy controls. In an
    Conclusion: JAK inhibition has a major effect on B cell activation and differentiation, with differential outcomes between JAK inhibitors hinting towards distinct and unique effects on B cell homeostasis.
    MeSH term(s) Humans ; Janus Kinase Inhibitors/pharmacology ; Janus Kinase Inhibitors/therapeutic use ; Immunomodulating Agents ; Arthritis, Rheumatoid/drug therapy ; Anti-Inflammatory Agents/pharmacology ; Cell Differentiation
    Chemical Substances Janus Kinase Inhibitors ; Immunomodulating Agents ; Anti-Inflammatory Agents
    Language English
    Publishing date 2023-01-26
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2023.1087986
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Physical Exercise Preserves Adult Visual Plasticity in Mice and Restores it after a Stroke in the Somatosensory Cortex.

    Kalogeraki, Evgenia / Pielecka-Fortuna, Justyna / Hüppe, Janika M / Löwel, Siegrid

    Frontiers in aging neuroscience

    2016  Volume 8, Page(s) 212

    Abstract: The primary visual cortex (V1) is widely used to study brain plasticity, which is not only crucial for normal brain function, such as learning and memory, but also for recovery after brain injuries such as stroke. In standard cage (SC) raised mice, ... ...

    Abstract The primary visual cortex (V1) is widely used to study brain plasticity, which is not only crucial for normal brain function, such as learning and memory, but also for recovery after brain injuries such as stroke. In standard cage (SC) raised mice, experience-dependent ocular dominance (OD) plasticity in V1 declines with age and is compromised by a lesion in adjacent and distant cortical regions. In contrast, mice raised in an enriched environment (EE), exhibit lifelong OD plasticity and are protected from losing OD plasticity after a stroke-lesion in the somatosensory cortex. Since SC mice with an access to a running wheel (RW) displayed preserved OD plasticity during aging, we investigated whether physical exercise might also provide a plasticity promoting effect after a cortical stroke. To this end, we tested if adult RW-raised mice preserved OD plasticity after stroke and also if short-term running after stroke restored OD plasticity to SC mice. Indeed, unlike mice without a RW, adult RW mice continued to show OD plasticity even after stroke, and a 2 weeks RW experience after stroke already restored lost OD plasticity. Additionally, the experience-enabled increase of the spatial frequency and contrast threshold of the optomotor reflex of the open eye, normally lost after a stroke, was restored in both groups of RW mice. Our data suggest that physical exercise alone can not only preserve visual plasticity into old age, but also restore it after a cortical stroke.
    Language English
    Publishing date 2016-09-21
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2558898-9
    ISSN 1663-4365
    ISSN 1663-4365
    DOI 10.3389/fnagi.2016.00212
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Abatacept modulates CD80 and CD86 expression and memory formation in human B-cells.

    Lorenzetti, Raquel / Janowska, Iga / Smulski, Cristian Roberto / Frede, Natalie / Henneberger, Nadine / Walter, Lea / Schleyer, Marei-Theresa / Hüppe, Janika M / Staniek, Julian / Salzer, Ulrich / Venhoff, Ana / Troilo, Arianna / Voll, Reinhard Edmund / Venhoff, Nils / Thiel, Jens / Rizzi, Marta

    Journal of autoimmunity

    2019  Volume 101, Page(s) 145–152

    Abstract: Background: Cytotoxic T lymphocyte antigen-4 (CTLA-4) limits T-cell activation and is expressed on T-regulatory cells. Human CTLA-4 deficiency results in severe immune dysregulation. Abatacept (CTLA-4 Ig) is approved for the treatment of rheumatoid ... ...

    Abstract Background: Cytotoxic T lymphocyte antigen-4 (CTLA-4) limits T-cell activation and is expressed on T-regulatory cells. Human CTLA-4 deficiency results in severe immune dysregulation. Abatacept (CTLA-4 Ig) is approved for the treatment of rheumatoid arthritis (RA) and its mechanism of action is attributed to effects on T-cells. It is known that CTLA-4 modulates the expression of its ligands CD80 and CD86 on antigen presenting cells (APC) by transendocytosis. As B-cells express CD80/CD86 and function as APC, we hypothesize that B-cells are a direct target of abatacept.
    Objectives: To investigate direct effects of abatacept on human B-lymphocytes in vitro and in RA patients.
    Methods: The effect of abatacept on healthy donor B-cells' phenotype, activation and CD80/CD86 expression was studied in vitro. Nine abatacept-treated RA patients were studied. Seven of these were followed up to 24 months, and two up to 12 months only and treatment response, immunoglobulins, ACPA, RF concentrations, B-cell phenotype and ACPA-specific switched memory B-cell frequency were assessed.
    Results: B-cell development was unaffected by abatacept. Abatacept treatment resulted in a dose-dependent decrease of CD80/CD86 expression on B-cells in vitro, which was due to dynamin-dependent internalization. RA patients treated with abatacept showed a progressive decrease in plasmablasts and serum IgG. While ACPA-titers only moderately declined, the frequency of ACPA-specific switched memory B-cells significantly decreased.
    Conclusions: Abatacept directly targets B-cells by reducing CD80/CD86 expression. Impairment of antigen presentation and T-cell activation may result in altered B-cell selection, providing a new therapeutic mechanism and a base for abatacept use in B-cell mediated autoimmunity.
    MeSH term(s) Abatacept/pharmacology ; Adult ; Aged ; Arthritis, Rheumatoid/genetics ; Arthritis, Rheumatoid/immunology ; Arthritis, Rheumatoid/metabolism ; Arthritis, Rheumatoid/pathology ; B-Lymphocytes/drug effects ; B-Lymphocytes/immunology ; B-Lymphocytes/metabolism ; B7-1 Antigen/metabolism ; B7-2 Antigen/metabolism ; Female ; Gene Expression ; Humans ; Immunoglobulin G/immunology ; Immunologic Memory/drug effects ; Immunophenotyping ; Lymphocyte Activation/drug effects ; Lymphocyte Activation/genetics ; Lymphocyte Activation/immunology ; Male ; Middle Aged
    Chemical Substances B7-1 Antigen ; B7-2 Antigen ; Immunoglobulin G ; Abatacept (7D0YB67S97)
    Language English
    Publishing date 2019-05-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639452-8
    ISSN 1095-9157 ; 0896-8411
    ISSN (online) 1095-9157
    ISSN 0896-8411
    DOI 10.1016/j.jaut.2019.04.016
    Database MEDical Literature Analysis and Retrieval System OnLINE

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