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  1. Article: Case report: JAK inhibition as promising treatment option of fatal RVCLS due to

    Ufer, Friederike / Ziegler, Susanne M / Altfeld, Marcus / Friese, Manuel A

    Frontiers in neurology

    2023  Volume 14, Page(s) 1118369

    Abstract: Introduction: Autosomal dominant mutations in the C-terminal part of : Methods: We collected clinical data of an extended family with RVCLS (: Results: We report clinical details from 29 family members with 17 of them showing RVCLS symptoms. ... ...

    Abstract Introduction: Autosomal dominant mutations in the C-terminal part of
    Methods: We collected clinical data of an extended family with RVCLS (
    Results: We report clinical details from 29 family members with 17 of them showing RVCLS symptoms. Treatment of the index patient with ruxolitinib for >4 years was well-tolerated and clinically stabilized RVCLS activity. Moreover, we noticed normalization of initially elevated
    Discussion: We provide evidence that JAK inhibition as RVCLS treatment appears safe and could slow clinical worsening in symptomatic adults. These results encourage further use of JAK inhibitors in affected individuals together with monitoring of
    Language English
    Publishing date 2023-02-21
    Publishing country Switzerland
    Document type Case Reports
    ZDB-ID 2564214-5
    ISSN 1664-2295
    ISSN 1664-2295
    DOI 10.3389/fneur.2023.1118369
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Reduction of IFN-I responses by plasmacytoid dendritic cells in a longitudinal trans men cohort.

    Grünhagel, Benjamin / Borggrewe, Malte / Hagen, Sven Hendrik / Ziegler, Susanne M / Henseling, Florian / Glau, Laura / Thiele, Rebecca-Jo / Pujantell, Maria / Sivayoganathan, Varshi / Padoan, Benedetta / Claussen, Janna M / Düsedau, Arne / Hennesen, Jana / Bunders, Madeleine J / Bonn, Stefan / Tolosa, Eva / Krebs, Christian F / Dorn, Christoph / Altfeld, Marcus

    iScience

    2023  Volume 26, Issue 11, Page(s) 108209

    Abstract: Type I interferons (IFN-I) are important mediators of antiviral immunity and autoimmune diseases. Female plasmacytoid dendritic cells (pDCs) exert an elevated capacity to produce IFN-I upon toll-like receptor 7 (TLR7) activation compared to male pDCs, ... ...

    Abstract Type I interferons (IFN-I) are important mediators of antiviral immunity and autoimmune diseases. Female plasmacytoid dendritic cells (pDCs) exert an elevated capacity to produce IFN-I upon toll-like receptor 7 (TLR7) activation compared to male pDCs, and both sex hormones and X-encoded genes have been implicated in these sex-specific differences. Using longitudinal samples from a trans men cohort receiving gender-affirming hormone therapy (GAHT), the impact of testosterone injections on TLR7-mediated IFN-I production by pDCs was assessed. Single-cell RNA analyses of pDCs showed downregulation of IFN-I-related gene expression signatures but also revealed transcriptional inter-donor heterogeneity. Longitudinal quantification showed continuous reduction of IFN-I protein production by pDCs and reduced expression of IFN-I-stimulated genes in peripheral blood mononuclear cells (PBMCs). These studies in trans men demonstrate that testosterone administration reduces IFN-I production by pDCs over time and provide insights into the immune-modulatory role of testosterone in sex-specific IFN-I-mediated immune responses.
    Language English
    Publishing date 2023-10-13
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2023.108209
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Human pDCs display sex-specific differences in type I interferon subtypes and interferon α/β receptor expression.

    Ziegler, Susanne M / Beisel, Claudia / Sutter, Kathrin / Griesbeck, Morgane / Hildebrandt, Heike / Hagen, Sven H / Dittmer, Ulf / Altfeld, Marcus

    European journal of immunology

    2017  Volume 47, Issue 2, Page(s) 251–256

    Abstract: The outcomes of many diseases differ between women and men, with women experiencing a higher incidence and more severe pathogenesis of autoimmune and some infectious diseases. It has been suggested that this is partially due to activation of plasmacytoid ...

    Abstract The outcomes of many diseases differ between women and men, with women experiencing a higher incidence and more severe pathogenesis of autoimmune and some infectious diseases. It has been suggested that this is partially due to activation of plasmacytoid dendritic cells (pDCs), the main producers of interferon (IFN)-α, in response to toll-like receptor (TLR)7 stimulation. We investigated the induction of type I IFN (IFN-I) subtypes upon TLR7 stimulation on isolated pDCs. Our data revealed a sex-specific differential expression of IFN-Is, with pDCs from females showing a significantly higher mRNA expression of all 13 IFN-α subtypes. In addition, pDCs from females had higher levels of IFN-β mRNA after stimulation, indicating that sex differences in IFN-I production by pDCs were mediated by a signaling event upstream of the first loop of IFN-I mRNA transcription. Furthermore, the surface expression levels of the common IFN-α/β receptor subunit 2 were significantly higher on pDCs from females in comparison to males. These data indicate that higher IFN-α production is already established at the mRNA level and propose a contribution of higher IFN-α/β receptor 2 expression on pDCs to the immunological differences in IFN-I production observed between females and males.
    MeSH term(s) Adult ; Cells, Cultured ; Dendritic Cells/physiology ; Female ; Humans ; Immunization ; Interferon Type I/genetics ; Interferon Type I/metabolism ; Male ; RNA, Messenger/genetics ; Receptor, Interferon alpha-beta/genetics ; Receptor, Interferon alpha-beta/metabolism ; Sex ; Sex Characteristics ; Signal Transduction ; Toll-Like Receptor 7/immunology ; Transcriptome
    Chemical Substances IFNAR2 protein, human ; Interferon Type I ; RNA, Messenger ; TLR7 protein, human ; Toll-Like Receptor 7 ; Receptor, Interferon alpha-beta (156986-95-7)
    Language English
    Publishing date 2017
    Publishing country Germany
    Document type Comparative Study ; Journal Article
    ZDB-ID 120108-6
    ISSN 1521-4141 ; 0014-2980
    ISSN (online) 1521-4141
    ISSN 0014-2980
    DOI 10.1002/eji.201646725
    Database MEDical Literature Analysis and Retrieval System OnLINE

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