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Your search keyword '"Joris P. Jansen"' showing total 4 results
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4 results on '"Joris P. Jansen"'

1. MEF2C opposes Notch in lymphoid lineage decision and drives leukemia in the thymus

Author

Kirsten Canté-Barrett, Mariska T. Meijer, Valentina Cordo’, Rico Hagelaar, Wentao Yang, Jiyang Yu, Willem K. Smits, Marloes E. Nulle, Joris P. Jansen, Rob Pieters, Jun J. Yang, Jody J. Haigh, Steven Goossens, and Jules P.P. Meijerink

Subjects
Hematology, Oncology, Medicine
Abstract

Rearrangements that drive ectopic MEF2C expression have recurrently been found in patients with human early thymocyte progenitor acute lymphoblastic leukemia (ETP-ALL). Here, we show high levels of MEF2C expression in patients with ETP-ALL. Using both in vivo and in vitro models of ETP-ALL, we demonstrate that elevated MEF2C expression blocks NOTCH-induced T cell differentiation while promoting a B-lineage program. MEF2C activates a B cell transcriptional program in addition to RUNX1, GATA3, and LMO2; upregulates the IL-7R; and boosts cell survival by upregulation of BCL2. MEF2C and the Notch pathway, therefore, demarcate opposite regulators of B- or T-lineage choices, respectively. Enforced MEF2C expression in mouse or human progenitor cells effectively blocks early T cell differentiation and promotes the development of biphenotypic lymphoid tumors that coexpress CD3 and CD19, resembling human mixed phenotype acute leukemia. Salt-inducible kinase (SIK) inhibitors impair MEF2C activity and alleviate the T cell developmental block. Importantly, this sensitizes cells to prednisolone treatment. Therefore, SIK-inhibiting compounds such as dasatinib are potentially valuable additions to standard chemotherapy for human ETP-ALL.

Published
2022
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2. Host–Receptor Post-Translational Modifications Refine Staphylococcal Leukocidin Cytotoxicity

Author

Angelino T. Tromp, Michiel Van Gent, Joris P. Jansen, Lisette M. Scheepmaker, Anneroos Velthuizen, Carla J.C. De Haas, Kok P.M. Van Kessel, Bart W. Bardoel, Michael Boettcher, Michael T. McManus, Jos A.G. Van Strijp, Robert Jan Lebbink, Pieter-Jan A. Haas, and András N. Spaan

Subjects
staphylococcus aureus, bi-component pore-forming toxins, leukocidins, receptors, g-protein coupled receptors, post-translational modifications, Medicine
Abstract

Staphylococcal bi-component pore-forming toxins, also known as leukocidins, target and lyse human phagocytes in a receptor-dependent manner. S-components of the leukocidins Panton-Valentine leukocidin (PVL), γ-haemolysin AB (HlgAB) and CB (HlgCB), and leukocidin ED (LukED) specifically employ receptors that belong to the class of G-protein coupled receptors (GPCRs). Although these receptors share a common structural architecture, little is known about the conserved characteristics of the interaction between leukocidins and GPCRs. In this study, we investigated host cellular pathways contributing to susceptibility towards S. aureus leukocidin cytotoxicity. We performed a genome-wide CRISPR/Cas9 library screen for toxin-resistance in U937 cells sensitized to leukocidins by ectopic expression of different GPCRs. Our screen identifies post-translational modification (PTM) pathways involved in the sulfation and sialylation of the leukocidin-receptors. Subsequent validation experiments show differences in the impact of PTM moieties on leukocidin toxicity, highlighting an additional layer of refinement and divergence in the staphylococcal host-pathogen interface. Leukocidin receptors may serve as targets for anti-staphylococcal interventions and understanding toxin-receptor interactions will facilitate the development of innovative therapeutics. Variations in the genes encoding PTM pathways could provide insight into observed differences in susceptibility of humans to infections with S. aureus.

Published
2020
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3. Human CD45 is an F-component-specific receptor for the staphylococcal toxin Panton-Valentine leukocidin

Author

Thomas Henry, Jos A. G. van Strijp, Pauline Abrial, Robert Jan Lebbink, Emilie Bourdonnay, Bart W. Bardoel, Gerard Lina, Kok P. M. van Kessel, François Vandenesch, Michael T. McManus, Angelino T. Tromp, Michiel van Gent, Elisabeth Kruse, Carla J. C. de Haas, Joris P Jansen, András N Spaan, Amandine Martin, Christopher J. Day, Michael P. Jennings, Michael Boettcher, Pieter-Jan A. Haas, University Medical Center [Utrecht], University of Chicago, Inflammasome, Infections bactériennes et autoinflammation, Inflammasome, Bacterial Infections and Autoinflammation (I2BA), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of California [San Francisco] (UCSF), University of California, Griffith University [Brisbane], Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Rockefeller University [New York], Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of California [San Francisco] (UC San Francisco), University of California (UC), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Microbiology (medical), Staphylococcus aureus, Neutrophils, 030106 microbiology, Immunology, Bacterial Toxins, Leukocidin, Exotoxins, Complement C5a, Biology, medicine.disease_cause, Applied Microbiology and Biotechnology, Microbiology, Cell Line, 03 medical and health sciences, Hemolysin Proteins, Mice, Bacterial Proteins, Leukocidins, Genetics, medicine, Animals, Humans, Receptor, skin and connective tissue diseases, Receptor, Anaphylatoxin C5a, Mice, Knockout, Toxin, Cell Biology, respiratory system, biochemical phenomena, metabolism, and nutrition, Staphylococcal Infections, bacterial infections and mycoses, Phenotype, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Bacterial Load, Disease Models, Animal, Cell culture, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, bacteria, [SDV.IMM]Life Sciences [q-bio]/Immunology, Leukocyte Common Antigens, Panton–Valentine leukocidin, CRISPR-Cas Systems, Cellular Tropism
Abstract

International audience; The staphylococcal bi-component leukocidins Panton-Valentine leukocidin (PVL) and γ-haemolysin CB (HlgCB) target human phagocytes. Binding of the toxins' S-components to human complement C5a receptor 1 (C5aR1) contributes to cellular tropism and human specificity of PVL and HlgCB. To investigate the role of both leukocidins during infection, we developed a human C5aR1 knock-in (hC5aR1KI) mouse model. HlgCB, but unexpectedly not PVL, contributed to increased bacterial loads in tissues of hC5aR1KI mice. Compared to humans, murine hC5aR1KI neutrophils showed a reduced sensitivity to PVL, which was mediated by the toxin's F-component LukF-PV. By performing a genome-wide CRISPR-Cas9 screen, we identified CD45 as a receptor for LukF-PV. The human-specific interaction between LukF-PV and CD45 provides a molecular explanation for resistance of hC5aR1KI mouse neutrophils to PVL and probably contributes to the lack of a PVL-mediated phenotype during infection in these mice. This study demonstrates an unsuspected role of the F-component in driving the sensitivity of human phagocytes to PVL.

Published
2017
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4. Publisher Correction: Human CD45 is an F-component-specific receptor for the staphylococcal toxin Panton–Valentine leukocidin

Author

Michiel van Gent, Gerard Lina, Bart W. Bardoel, Michael T. McManus, Carla J. C. de Haas, Robert Jan Lebbink, Jos A. G. van Strijp, Elisabeth Kruse, Thomas Henry, Amandine Martin, Pauline Abrial, Christopher J. Day, François Vandenesch, Kok P. M. van Kessel, András N Spaan, Joris P Jansen, Pieter-Jan A. Haas, Michael Boettcher, Michael P. Jennings, Emilie Bourdonnay, and Angelino T. Tromp

Subjects
0301 basic medicine, Microbiology (medical), Genetics, Immunology, Cell Biology, Biology, Applied Microbiology and Biotechnology, Microbiology, Citation database, 03 medical and health sciences, 030104 developmental biology, Component (UML), Staphylococcal toxin, Panton–Valentine leukocidin
Abstract

In the version of this Article originally published, the name of author Robert Jan Lebbink was coded wrongly, resulting in it being incorrect when exported to citation databases. This has now been corrected, though no visible changes will be apparent.

Published
2018
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