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  1. Article ; Online: In vitro triple coculture with gut microbiota from spondyloarthritis patients is characterized by inter-individual differences in inflammatory responses

    Annelore Beterams / Marta Calatayud Arroyo / Kim De Paepe / Ann-Sophie De Craemer / Dirk Elewaut / Koen Venken / Tom Van de Wiele

    Scientific Reports, Vol 12, Iss 1, Pp 1-

    2022  Volume 13

    Abstract: Abstract Spondyloarthritis is a group of chronic inflammatory diseases that primarily affects axial or peripheral joints and is frequently associated with inflammation at non-articular sites. The disease is multifactorial, involving genetics, immunity ... ...

    Abstract Abstract Spondyloarthritis is a group of chronic inflammatory diseases that primarily affects axial or peripheral joints and is frequently associated with inflammation at non-articular sites. The disease is multifactorial, involving genetics, immunity and environmental factors, including the gut microbiota. In vivo, microbiome contributions are difficult to assess due to the multifactorial disease complexity. In a proof-of-concept approach, we therefore used a triple coculture model of immune-like, goblet and epithelial cells to investigate whether we could detect a differential impact from spondyloarthritis- vs. healthy-derived gut microbiota on host cell response. Despite their phylogenetic resemblance, flow cytometry-based phenotypic clustering revealed human-derived gut microbiota from healthy origin to cluster together and apart from spondyloarthritis donors. At host level, mucus production was higher upon exposure to healthy microbiota. Pro-inflammatory cytokine responses displayed more inter-individual variability in spondyloarthritis than in healthy donors. Interestingly, the high dominance in the initial sample of one patient of Prevotella, a genus previously linked to spondyloarthritis, resulted in the most differential host response upon 16 h host-microbe coincubation. While future research should further focus on inter-individual variability by using gut microbiota from a large cohort of patients, this study underscores the importance of the gut microbiota during the SpA disease course.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2022-06-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Altered thymic differentiation and modulation of arthritis by invariant NKT cells expressing mutant ZAP70

    Meng Zhao / Mattias N. D. Svensson / Koen Venken / Ashu Chawla / Shu Liang / Isaac Engel / Piotr Mydel / Jeremy Day / Dirk Elewaut / Nunzio Bottini / Mitchell Kronenberg

    Nature Communications, Vol 9, Iss 1, Pp 1-

    2018  Volume 17

    Abstract: Invariant natural killer T (iNKT) cells can be subsetted based on their cytokine productions. Here the authors show, using Zap70 mutant mice, that interferon-γ secreting (IFN-γ) iNKT cells may be induced by hampered T cell receptor signallings to help ... ...

    Abstract Invariant natural killer T (iNKT) cells can be subsetted based on their cytokine productions. Here the authors show, using Zap70 mutant mice, that interferon-γ secreting (IFN-γ) iNKT cells may be induced by hampered T cell receptor signallings to help ameliorate interleukin-17-mediated joint inflammation.
    Keywords Science ; Q
    Language English
    Publishing date 2018-07-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Altered thymic differentiation and modulation of arthritis by invariant NKT cells expressing mutant ZAP70

    Meng Zhao / Mattias N. D. Svensson / Koen Venken / Ashu Chawla / Shu Liang / Isaac Engel / Piotr Mydel / Jeremy Day / Dirk Elewaut / Nunzio Bottini / Mitchell Kronenberg

    Nature Communications, Vol 9, Iss 1, Pp 1-

    2018  Volume 17

    Abstract: Invariant natural killer T (iNKT) cells can be subsetted based on their cytokine productions. Here the authors show, using Zap70 mutant mice, that interferon-γ secreting (IFN-γ) iNKT cells may be induced by hampered T cell receptor signallings to help ... ...

    Abstract Invariant natural killer T (iNKT) cells can be subsetted based on their cytokine productions. Here the authors show, using Zap70 mutant mice, that interferon-γ secreting (IFN-γ) iNKT cells may be induced by hampered T cell receptor signallings to help ameliorate interleukin-17-mediated joint inflammation.
    Keywords Science ; Q
    Language English
    Publishing date 2018-07-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: An in silico approach for modelling T-helper polarizing iNKT cell agonists.

    Anton De Spiegeleer / Evelien Wynendaele / Matthias Vandekerckhove / Sofie Stalmans / Maxime Boucart / Nele Van Den Noortgate / Koen Venken / Serge Van Calenbergh / Sandrine Aspeslagh / Dirk Elewaut

    PLoS ONE, Vol 9, Iss 1, p e

    2014  Volume 87000

    Abstract: Many analogues of the glycolipid alpha-galactosylceramide (α-GalCer) are known to activate iNKT cells through their interaction with CD1d-expressing antigen-presenting cells, inducing the release of Th1 and Th2 cytokines. Because of iNKT cell involvement ...

    Abstract Many analogues of the glycolipid alpha-galactosylceramide (α-GalCer) are known to activate iNKT cells through their interaction with CD1d-expressing antigen-presenting cells, inducing the release of Th1 and Th2 cytokines. Because of iNKT cell involvement and associated Th1/Th2 cytokine changes in a broad spectrum of human diseases, the design of iNKT cell ligands with selective Th1 and Th2 properties has been the subject of extensive research. This search for novel iNKT cell ligands requires refined structural insights. Here we will visualize the chemical space of 333 currently known iNKT cell activators, including several newly tested analogues, by more than 3000 chemical descriptors which were calculated for each individual analogue. To evaluate the immunological responses we analyzed five different cytokines in five different test-systems. We linked the chemical space to the immunological space using a system biology computational approach resulting in highly sensitive and specific predictive models. Moreover, these models correspond with the current insights of iNKT cell activation by α-GalCer analogues, explaining the Th1 and Th2 biased responses, downstream of iNKT cell activation. We anticipate that such models will be of great value for the future design of iNKT cell agonists.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2014-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: RORγt inhibition selectively targets IL-17 producing iNKT and γδ-T cells enriched in Spondyloarthritis patients

    Koen Venken / Peggy Jacques / Céline Mortier / Mark E. Labadia / Tine Decruy / Julie Coudenys / Kathleen Hoyt / Anita L. Wayne / Robert Hughes / Michael Turner / Sofie Van Gassen / Liesbet Martens / Dustin Smith / Christian Harcken / Joseph Wahle / Chao-Ting Wang / Eveline Verheugen / Nadia Schryvers / Gaëlle Varkas /
    Heleen Cypers / Ruth Wittoek / Yves Piette / Lieve Gyselbrecht / Serge Van Calenbergh / Filip Van den Bosch / Yvan Saeys / Gerald Nabozny / Dirk Elewaut

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 15

    Abstract: The role of innate T cell subsets in the pathogenesis of spondyloarthritis (SpA) is not well understood. Here, the authors examine the role of invariant natural killer T (iNKT) and γδ-T cells in SpA and show that disease-derived iNKT and γδ-T cells have ... ...

    Abstract The role of innate T cell subsets in the pathogenesis of spondyloarthritis (SpA) is not well understood. Here, the authors examine the role of invariant natural killer T (iNKT) and γδ-T cells in SpA and show that disease-derived iNKT and γδ-T cells have unique and Th17-skewed phenotype and gene expression profiles within inflamed joints.
    Keywords Science ; Q
    Language English
    Publishing date 2019-01-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: RORγt inhibition selectively targets IL-17 producing iNKT and γδ-T cells enriched in Spondyloarthritis patients

    Koen Venken / Peggy Jacques / Céline Mortier / Mark E. Labadia / Tine Decruy / Julie Coudenys / Kathleen Hoyt / Anita L. Wayne / Robert Hughes / Michael Turner / Sofie Van Gassen / Liesbet Martens / Dustin Smith / Christian Harcken / Joseph Wahle / Chao-Ting Wang / Eveline Verheugen / Nadia Schryvers / Gaëlle Varkas /
    Heleen Cypers / Ruth Wittoek / Yves Piette / Lieve Gyselbrecht / Serge Van Calenbergh / Filip Van den Bosch / Yvan Saeys / Gerald Nabozny / Dirk Elewaut

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 15

    Abstract: The role of innate T cell subsets in the pathogenesis of spondyloarthritis (SpA) is not well understood. Here, the authors examine the role of invariant natural killer T (iNKT) and γδ-T cells in SpA and show that disease-derived iNKT and γδ-T cells have ... ...

    Abstract The role of innate T cell subsets in the pathogenesis of spondyloarthritis (SpA) is not well understood. Here, the authors examine the role of invariant natural killer T (iNKT) and γδ-T cells in SpA and show that disease-derived iNKT and γδ-T cells have unique and Th17-skewed phenotype and gene expression profiles within inflamed joints.
    Keywords Science ; Q
    Language English
    Publishing date 2019-01-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article: Leptin’s metabolic and immune functions can be uncoupled at the ligand/receptor interaction level

    Zabeau, Lennart / Cathy J. Jensen / Sylvie Seeuws / Koen Venken / Annick Verhee / Dominiek Catteeuw / Geert van Loo / Hui Chen / Ken Walder / Jacob Hollis / Simon Foote / Margaret J. Morris / José Van der Heyden / Frank Peelman / Brian J. Oldfield / Justin P. Rubio / Dirk Elewaut / Jan Tavernier

    Cellular and molecular life sciences. 2015 Feb., v. 72, no. 3

    2015  

    Abstract: The adipocyte-derived cytokine leptin acts as a metabolic switch, connecting the body’s metabolism to high-energy consuming processes such as reproduction and immune responses. We here provide genetic and biochemical evidence that the metabolic and ... ...

    Abstract The adipocyte-derived cytokine leptin acts as a metabolic switch, connecting the body’s metabolism to high-energy consuming processes such as reproduction and immune responses. We here provide genetic and biochemical evidence that the metabolic and immune functions of leptin can be uncoupled at the receptor level. First, homozygous mutant fatt/fatt mice carry a spontaneous splice mutation causing deletion of the leptin receptor (LR) immunoglobulin-like domain (IGD) in all LR isoforms. These mice are hyperphagic and morbidly obese, but display only minimal changes in size and cellularity of the thymus, and cellular immune responses are unaffected. These animals also displayed liver damage in response to concavalin A comparable to wild-type and heterozygous littermates. Second, treatment of healthy mice with a neutralizing nanobody targeting IGD induced weight gain and hyperinsulinaemia, but completely failed to block development of experimentally induced autoimmune diseases. These data indicate that leptin receptor deficiency or antagonism profoundly affects metabolism, with little concomitant effects on immune functions.
    Keywords autoimmune diseases ; cell-mediated immunity ; cytokines ; heterozygosity ; homozygosity ; hyperinsulinemia ; immune response ; leptin ; leptin receptors ; liver ; metabolism ; mice ; mutants ; mutation ; neutralization ; reproduction ; thymus gland ; weight gain
    Language English
    Dates of publication 2015-02
    Size p. 629-644.
    Publishing place Springer Basel
    Document type Article
    ZDB-ID 1358415-7
    ISSN 1420-9071 ; 1420-682X
    ISSN (online) 1420-9071
    ISSN 1420-682X
    DOI 10.1007/s00018-014-1697-x
    Database NAL-Catalogue (AGRICOLA)

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