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2. Effect of anti-interleukin drugs in patients with COVID-19 and signs of cytokine release syndrome (COV-AID): a factorial, randomised, controlled trial

Author

Declercq, Jozefien, Van Damme, Karel F A, De Leeuw, Elisabeth, Maes, Bastiaan, Bosteels, Cedric, Tavernier, Simon J, De Buyser, Stefanie, Colman, Roos, Hites, Maya, Verschelden, Gil, Fivez, Tom, Moerman, Filip, Demedts, Ingel K, Dauby, Nicolas, De Schryver, Nicolas, Govaerts, Elke, Vandecasteele, Stefaan J, Van Laethem, Johan, Anguille, Sebastien, van der Hilst, Jeroen, Misset, Benoit, Slabbynck, Hans, Wittebole, Xavier, Liénart, Fabienne, Legrand, Catherine, Buyse, Marc, Stevens, Dieter, Bauters, Fre, Seys, Leen J M, Aegerter, Helena, Smole, Ursula, Bosteels, Victor, Hoste, Levi, Naesens, Leslie, Haerynck, Filomeen, Vandekerckhove, Linos, Depuydt, Pieter, van Braeckel, Eva, Rottey, Sylvie, Peene, Isabelle, Van Der Straeten, Catherine, Hulstaert, Frank, and Lambrecht, Bart N more...

Published
2021
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6. Crosstalk between memory B cells and fibroblasts contributes to COPD pathogenesis

Author

Jacobs, Merel, primary, Anckaert, Jasper, additional, Faiz, Alen, additional, Van Gaever, Femke, additional, Verschraegen, Sven, additional, Salhi, Bihiyga, additional, Schynkel, Tinus, additional, Venken, Koen, additional, Elewaut, Dirk, additional, Hansbro, Phil, additional, Brusselle, Guy, additional, Mestdagh, Pieter, additional, Seys, Leen, additional, and Bracke, Ken, additional more...

Published
2023
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7. Ostertagia ostertagi activation-associated secreted protein 1 (OSP-2) mRNA, complete cds.

Author

Zwanenburg, Laurens, Borloo, Jimmy, Decorte, Bregt, Bunte, Myrna, Mokhtari, Sanaz, Serna, Sonia, Reichardt, Niels C., Seys, Leen J.M., van Diepen, Angela, Schots, Arjen, Wilbers, Ruud, Hokke, Cornelis H., Claerebout, Edwin, Geldhof, Peter, Zwanenburg, Laurens, Borloo, Jimmy, Decorte, Bregt, Bunte, Myrna, Mokhtari, Sanaz, Serna, Sonia, Reichardt, Niels C., Seys, Leen J.M., van Diepen, Angela, Schots, Arjen, Wilbers, Ruud, Hokke, Cornelis H., Claerebout, Edwin, and Geldhof, Peter more...

Published
2023

9. TIM3+ TRBV11-2 T cells and IFNγ signature in patrolling monocytes and CD16+ NK cells delineate MIS-C

Author

MIS-C Clinicians, Hoste, Levi, Roels, Lisa, Naesens, Leslie, Bosteels, Victor, Vanhee, Stijn, Dupont, Sam, Bosteels, Cedric, Browaeys, Robin, Vandamme, Niels, Verstaen, Kevin, Roels, Jana, Van Damme, Karel F A, Maes, Bastiaan, De Leeuw, Elisabeth, Declercq, Jozefien, Aegerter, Helena, Seys, Leen, Smole, Ursula, De Prijck, Sofie, Vanheerswynghels, Manon, Claes, Karlien, Debacker, Veronique, Van Isterdael, Gert, Backers, Lynn, Claes, Kathleen B M, Bastard, Paul, Jouanguy, Emmanuelle, Zhang, Shen-Ying, Mets, Gilles, Dehoorne, Joke, Vandekerckhove, Kristof, Schelstraete, Petra, Willems, Jef, Stordeur, Patrick, Janssens, Sophie, Beyaert, Rudi, Saeys, Yvan, Casanova, Jean-Laurent, Lambrecht, Bart N, Haerynck, Filomeen, Tavernier, Simon J, Daelemans, Siel, Pulmonary Medicine, Clinical sciences, Growth and Development, and Pediatrics more...

Subjects
Male, T-Lymphocytes, CHILDREN, LIPOPOLYSACCHARIDE, infectious diseases, Lymphocyte Activation, HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS, DISEASE, pediatric SARS-CoV-2 infection, Monocytes, Cohort Studies, IFNγ signature, TIM3+ TRBV11-2 T cells, Medicine and Health Sciences, Immunology and Allergy, immunodysregulation syndrome, Child, Complement Activation, Hepatitis A Virus Cellular Receptor 2, Interleukin-15, B-Lymphocytes, Superantigens, Patrolling, hemic and immune systems, Systemic Inflammatory Response Syndrome, Cell biology, Killer Cells, Natural, Interferon Type I, SHOCK, Cytokines, Female, Adolescent, MULTISYSTEM INFLAMMATORY SYNDROME, Immunology, Receptors, Antigen, T-Cell, CD16+ NK cells, MIS-C, SARS-COV-2, CD16, Biology, Article, Infectious Disease and Host Defense, Interferon-gamma, Humans, Pediatrics, Perinatology, and Child Health, Cell Proliferation, Inflammation, INTERFERON-GAMMA, SARS-CoV-2, Receptors, IgG, Biology and Life Sciences, COVID-19, Immunity, Humoral, Enterocytes, patrolling monocytes, BARRIER FUNCTION, Alveolar Epithelial Cells, Blood Vessels, Signature (topology)
Abstract

MIS-C is a novel immunodysregulation syndrome in children with a history of SARS-CoV-2 infection. This study employs a multi-omics approach to explore its immunopathogenesis. The authors show that IFNγ-mediated interactions between T cells, monocytes, and NK cells reside at the heart of the disease., In rare instances, pediatric SARS-CoV-2 infection results in a novel immunodysregulation syndrome termed multisystem inflammatory syndrome in children (MIS-C). We compared MIS-C immunopathology with severe COVID-19 in adults. MIS-C does not result in pneumocyte damage but is associated with vascular endotheliitis and gastrointestinal epithelial injury. In MIS-C, the cytokine release syndrome is characterized by IFNγ and not type I interferon. Persistence of patrolling monocytes differentiates MIS-C from severe COVID-19, which is dominated by HLA-DRlo classical monocytes. IFNγ levels correlate with granzyme B production in CD16+ NK cells and TIM3 expression on CD38+/HLA-DR+ T cells. Single-cell TCR profiling reveals a skewed TCRβ repertoire enriched for TRBV11-2 and a superantigenic signature in TIM3+/CD38+/HLA-DR+ T cells. Using NicheNet, we confirm IFNγ as a central cytokine in the communication between TIM3+/CD38+/HLA-DR+ T cells, CD16+ NK cells, and patrolling monocytes. Normalization of IFNγ, loss of TIM3, quiescence of CD16+ NK cells, and contraction of patrolling monocytes upon clinical resolution highlight their potential role in MIS-C immunopathogenesis., Graphical Abstract more...

Published
2021
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Author

Hoste, Levi, Roels, Lisa, Naesens, Leslie, Bosteels, Victor, Vanhee, Stijn, Dupont, Sam, Bosteels, Cedric, Browaeys, Robin, Vandamme, Niels, Verstaen, Kevin, Roels, Jana, Van Damme, Karel F.A., Maes, Bastiaan, De Leeuw, Elisabeth, Declercq, Jozefien, Aegerter, Helena, Seys, Leen, Smole, Ursula, De Prijck, Sofie, Vanheerswynghels, Manon, Claes, Karlien, Debacker, Veronique, Van Isterdael, Gert, Backers, Lynn, Claes, Kathleen B.M., Bastard, Paul, Jouanguy, Emmanuelle, Zhang, Shen Ying, Mets, Gilles, Dehoorne, Joke, Vandekerckhove, Kristof, Schelstraete, Petra, Willems, Jef, Stordeur, Patrick, Janssens, Sophie, Beyaert, Rudi, Saeys, Yvan, Casanova, Jean Laurent, Lambrecht, Bart N., Haerynck, Filomeen, Tavernier, Simon J., Hoste, Levi, Roels, Lisa, Naesens, Leslie, Bosteels, Victor, Vanhee, Stijn, Dupont, Sam, Bosteels, Cedric, Browaeys, Robin, Vandamme, Niels, Verstaen, Kevin, Roels, Jana, Van Damme, Karel F.A., Maes, Bastiaan, De Leeuw, Elisabeth, Declercq, Jozefien, Aegerter, Helena, Seys, Leen, Smole, Ursula, De Prijck, Sofie, Vanheerswynghels, Manon, Claes, Karlien, Debacker, Veronique, Van Isterdael, Gert, Backers, Lynn, Claes, Kathleen B.M., Bastard, Paul, Jouanguy, Emmanuelle, Zhang, Shen Ying, Mets, Gilles, Dehoorne, Joke, Vandekerckhove, Kristof, Schelstraete, Petra, Willems, Jef, Stordeur, Patrick, Janssens, Sophie, Beyaert, Rudi, Saeys, Yvan, Casanova, Jean Laurent, Lambrecht, Bart N., Haerynck, Filomeen, and Tavernier, Simon J. more...

Published
2021

13. ADAR1 interaction with Z-RNA promotes editing of endogenous double-stranded RNA and prevents MDA5-dependent immune activation

Author

de Reuver, Richard, primary, Dierick, Evelien, additional, Wiernicki, Bartosz, additional, Staes, Katrien, additional, Seys, Leen, additional, De Meester, Ellen, additional, Muyldermans, Tuur, additional, Botzki, Alexander, additional, Lambrecht, Bart, additional, Van Nieuwerburgh, Filip, additional, Vandenabeele, Peter, additional, and Maelfait, Jonathan, additional more...

Published
2020
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14. Human lung CD1c dendritic cells orchestrate lymphoid neogenesis during COPD

Author

Naessens, Thomas, primary, Morias, Yannick, additional, Hamrud, Eva, additional, Gehrmann, Ulf, additional, Mattsson, Johan, additional, Skogberg, Gabriel, additional, Israelsson, Elisabeth, additional, Thörn, Kristofer, additional, Melville, Faye, additional, Seys, Leen, additional, Bracke, Ken, additional, Staples, Karl, additional, Cunoosamy, Danen, additional, Brusselle, Guy, additional, and Lambrecht, Bart, additional more...

Published
2019
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15. DPP4, the MERS coronavirus receptor, is upregulated in lungs of smokers and COPD patients

Author

Seys, Leen JM, Widagdo, W, Verhamme, Fien M, Kleinjan, Alex, Janssens, Wim, Joos, Guy F, Bracke, Ken R, Haagmans, Bart L, and Brusselle, Guy G

Subjects
respiratory system, respiratory tract diseases
Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) causes pneumonia with a relatively high case fatality rate in humans. Smokers and chronic obstructive pulmonary disease (COPD) patients have been reported to be more susceptible to MERS-CoV infection. Here, we determined the expression of MERS-CoV receptor, dipeptidyl peptidase IV (DPP4), in lung tissues of smokers without airflow limitation and COPD patients in comparison to non-smoking individuals (never-smokers). ispartof: Clinical Infectious Diseases vol:66 issue:1 pages:45-53 ispartof: location:United States status: published more...

Published
2018
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21. Association of innate defense proteins BPIFA1 and BPIFB1 with disease severity in COPD

Author

De Smet,Elise G, Seys,Leen JM, Verhamme,Fien M, Vanaudenaerde,Bart M, Brusselle,Guy G, Bingle,Colin D, Bracke,Ken R, De Smet,Elise G, Seys,Leen JM, Verhamme,Fien M, Vanaudenaerde,Bart M, Brusselle,Guy G, Bingle,Colin D, and Bracke,Ken R more...

Abstract

Elise G De Smet,1 Leen JM Seys,1,2 Fien M Verhamme,1 Bart M Vanaudenaerde,3 Guy G Brusselle,1 Colin D Bingle,4 Ken R Bracke1 1Laboratory for Translational Research in Obstructive Pulmonary Diseases, Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium; ²Laboratory of Immunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, Belgium; 3Laboratory for Respiratory Diseases, Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium; 4Academic Unit of Respiratory Medicine, Department of Infection, Immunity and Cardiovascular Disease, The University of Sheffield, Sheffield, UK Abstract: Chronic obstructive pulmonary disease (COPD) is characterized by an abnormal inflammatory response in the lungs caused by the inhalation of noxious particles and gases. The airway epithelium has a protective function against these harmful agents by maintaining a physical barrier and by secreting defensive proteins, such as bactericidal/permeability-increasing fold-containing (BPIF) proteins, BPIFA1 and BPIFB1. However, inconsistent data regarding BPIFA1 expression in smokers and COPD patients have been reported to date. Therefore, we investigated the expression of BPIFA1 and BPIFB1 in a large cohort of never-smokers and smokers with and without COPD, both on the messenger RNA (mRNA) level in lung tissue and on the protein level in airway epithelium. Furthermore, we examined the correlation between BPIFA1 and BPIFB1 levels, goblet cell hyperplasia, and lung function measurements. BPIFA1 and BPIFB1 mRNA expressions were significantly increased in stage III–IV COPD patients compared with stage II COPD patients and subjects without COPD. In addition, protein levels in COPD patients were significantly increased in comparison with subjects without COPD. BPIFA1 and BPIFB1 levels were inversely correlated with measurements of airflow limitation and positively correlated with goblet cell hyperplasia. In more...

Published
2017

27. TIM3+ TRBV11-2 T cells and IFNγ signature in patrolling monocytes and CD16+ NK cells delineate MIS-C

Author

Hoste, Levi, Roels, Lisa, Naesens, Leslie, Bosteels, Victor, Vanhee, Stijn, Dupont, Sam, Bosteels, Cedric, Browaeys, Robin, Vandamme, Niels, Verstaen, Kevin, Roels, Jana, Van Damme, Karel F.A., Maes, Bastiaan, De Leeuw, Elisabeth, Declercq, Jozefien, Aegerter, Helena, Seys, Leen, Smole, Ursula, De Prijck, Sofie, Vanheerswynghels, Manon, Claes, Karlien, Debacker, Veronique, Van Isterdael, Gert, Backers, Lynn, Claes, Kathleen B.M., Bastard, Paul, Jouanguy, Emmanuelle, Zhang, Shen-Ying, Mets, Gilles, Dehoorne, Joke, Vandekerckhove, Kristof, Schelstraete, Petra, Willems, Jef, Stordeur, Patrick, Janssens, Sophie, Beyaert, Rudi, Saeys, Yvan, Casanova, Jean-Laurent, Lambrecht, Bart N., Haerynck, Filomeen, and Tavernier, Simon J. more...

Abstract

In rare instances, pediatric SARS-CoV-2 infection results in a novel immunodysregulation syndrome termed multisystem inflammatory syndrome in children (MIS-C). We compared MIS-C immunopathology with severe COVID-19 in adults. MIS-C does not result in pneumocyte damage but is associated with vascular endotheliitis and gastrointestinal epithelial injury. In MIS-C, the cytokine release syndrome is characterized by IFNγ and not type I interferon. Persistence of patrolling monocytes differentiates MIS-C from severe COVID-19, which is dominated by HLA-DRlo classical monocytes. IFNγ levels correlate with granzyme B production in CD16+ NK cells and TIM3 expression on CD38+/HLA-DR+ T cells. Single-cell TCR profiling reveals a skewed TCRβ repertoire enriched for TRBV11-2 and a superantigenic signature in TIM3+/CD38+/HLA-DR+ T cells. Using NicheNet, we confirm IFNγ as a central cytokine in the communication between TIM3+/CD38+/HLA-DR+ T cells, CD16+ NK cells, and patrolling monocytes. Normalization of IFNγ, loss of TIM3, quiescence of CD16+ NK cells, and contraction of patrolling monocytes upon clinical resolution highlight their potential role in MIS-C immunopathogenesis. more...

Published
2022
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