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TIM3+ TRBV11-2 T cells and IFNγ signature in patrolling monocytes and CD16+ NK cells delineate MIS-C.
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 L; Primary Immune Deficiency Research Laboratory, Department of Internal Diseases and Pediatrics, Centre for Primary Immunodeficiency Ghent, Jeffrey Modell Diagnosis and Research Centre, Ghent University, Ghent, Belgium.
  • Roels L; Department of Internal Medicine and Pediatrics, Division of Pediatric Pulmonology, Infectious Diseases and Inborn Errors of Immunity, Ghent University Hospital, Ghent, Belgium.
  • Naesens L; Primary Immune Deficiency Research Laboratory, Department of Internal Diseases and Pediatrics, Centre for Primary Immunodeficiency Ghent, Jeffrey Modell Diagnosis and Research Centre, Ghent University, Ghent, Belgium.
  • Bosteels V; Department of Internal Medicine and Pediatrics, Division of Pediatric Pulmonology, Infectious Diseases and Inborn Errors of Immunity, Ghent University Hospital, Ghent, Belgium.
  • Vanhee S; Primary Immune Deficiency Research Laboratory, Department of Internal Diseases and Pediatrics, Centre for Primary Immunodeficiency Ghent, Jeffrey Modell Diagnosis and Research Centre, Ghent University, Ghent, Belgium.
  • Dupont S; Department of Internal Medicine and Pediatrics, Division of Pediatric Pulmonology, Infectious Diseases and Inborn Errors of Immunity, Ghent University Hospital, Ghent, Belgium.
  • Bosteels C; Department of Internal Medicine and Pediatrics, Ghent University Hospital, Ghent, Belgium.
  • Browaeys R; Center for Inflammation Research, Laboratory for Endoplasmic Reticulum Stress and Inflammation, VIB, Ghent, Belgium.
  • Vandamme N; Department of Internal Medicine and Pediatrics, Ghent University Hospital, Ghent, Belgium.
  • Verstaen K; Center for Inflammation Research, Laboratory of Immunoregulation and Mucosal Immunology, VIB Center for Inflammation Research, Ghent, Belgium.
  • Roels J; Department of Internal Medicine and Pediatrics, Ghent University Hospital, Ghent, Belgium.
  • Van Damme KFA; Center for Inflammation Research, Laboratory of Immunoregulation and Mucosal Immunology, VIB Center for Inflammation Research, Ghent, Belgium.
  • Maes B; Department of Internal Medicine and Pediatrics, Ghent University Hospital, Ghent, Belgium.
  • De Leeuw E; Center for Inflammation Research, Laboratory of Immunoregulation and Mucosal Immunology, VIB Center for Inflammation Research, Ghent, Belgium.
  • Declercq J; Data Mining and Modeling for Biomedicine, VIB Center for Inflammation Research, Ghent, Belgium.
  • Aegerter H; Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium.
  • Seys L; Data Mining and Modeling for Biomedicine, VIB Center for Inflammation Research, Ghent, Belgium.
  • Smole U; Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium.
  • De Prijck S; Data Mining and Modeling for Biomedicine, VIB Center for Inflammation Research, Ghent, Belgium.
  • Vanheerswynghels M; Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium.
  • Claes K; Data Mining and Modeling for Biomedicine, VIB Center for Inflammation Research, Ghent, Belgium.
  • Debacker V; Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium.
  • Van Isterdael G; Department of Internal Medicine and Pediatrics, Ghent University Hospital, Ghent, Belgium.
  • Backers L; Center for Inflammation Research, Laboratory of Immunoregulation and Mucosal Immunology, VIB Center for Inflammation Research, Ghent, Belgium.
  • Claes KBM; Department of Internal Medicine and Pediatrics, Ghent University Hospital, Ghent, Belgium.
  • Bastard P; Center for Inflammation Research, Laboratory of Immunoregulation and Mucosal Immunology, VIB Center for Inflammation Research, Ghent, Belgium.
  • Jouanguy E; Department of Internal Medicine and Pediatrics, Ghent University Hospital, Ghent, Belgium.
  • Zhang SY; Center for Inflammation Research, Laboratory of Immunoregulation and Mucosal Immunology, VIB Center for Inflammation Research, Ghent, Belgium.
  • Mets G; Department of Internal Medicine and Pediatrics, Ghent University Hospital, Ghent, Belgium.
  • Dehoorne J; Center for Inflammation Research, Laboratory of Immunoregulation and Mucosal Immunology, VIB Center for Inflammation Research, Ghent, Belgium.
  • Vandekerckhove K; Department of Internal Medicine and Pediatrics, Ghent University Hospital, Ghent, Belgium.
  • Schelstraete P; Center for Inflammation Research, Laboratory of Immunoregulation and Mucosal Immunology, VIB Center for Inflammation Research, Ghent, Belgium.
  • Willems J; Department of Internal Medicine and Pediatrics, Ghent University Hospital, Ghent, Belgium.
  • Stordeur P; Department of Internal Medicine and Pediatrics, Ghent University Hospital, Ghent, Belgium.
  • Janssens S; Center for Inflammation Research, Laboratory of Immunoregulation and Mucosal Immunology, VIB Center for Inflammation Research, Ghent, Belgium.
  • Beyaert R; Department of Internal Medicine and Pediatrics, Ghent University Hospital, Ghent, Belgium.
  • Saeys Y; Center for Inflammation Research, Laboratory of Immunoregulation and Mucosal Immunology, VIB Center for Inflammation Research, Ghent, Belgium.
  • Casanova JL; Department of Internal Medicine and Pediatrics, Ghent University Hospital, Ghent, Belgium.
  • Lambrecht BN; Center for Inflammation Research, Laboratory of Immunoregulation and Mucosal Immunology, VIB Center for Inflammation Research, Ghent, Belgium.
  • Haerynck F; Primary Immune Deficiency Research Laboratory, Department of Internal Diseases and Pediatrics, Centre for Primary Immunodeficiency Ghent, Jeffrey Modell Diagnosis and Research Centre, Ghent University, Ghent, Belgium.
  • Tavernier SJ; Department of Internal Medicine and Pediatrics, Division of Pediatric Pulmonology, Infectious Diseases and Inborn Errors of Immunity, Ghent University Hospital, Ghent, Belgium.
J Exp Med ; 219(2)2022 02 07.
Article in English | MEDLINE | ID: covidwho-1984990
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 TCRß 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.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Killer Cells, Natural / Monocytes / T-Lymphocytes / Interferon-gamma / Receptors, IgG / Systemic Inflammatory Response Syndrome / Hepatitis A Virus Cellular Receptor 2 / COVID-19 Type of study: Cohort study / Observational study / Prognostic study Topics: Long Covid Limits: Adolescent / Child / Female / Humans / Male Language: English Year: 2022 Document Type: Article Affiliation country: Jem.20211381

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Killer Cells, Natural / Monocytes / T-Lymphocytes / Interferon-gamma / Receptors, IgG / Systemic Inflammatory Response Syndrome / Hepatitis A Virus Cellular Receptor 2 / COVID-19 Type of study: Cohort study / Observational study / Prognostic study Topics: Long Covid Limits: Adolescent / Child / Female / Humans / Male Language: English Year: 2022 Document Type: Article Affiliation country: Jem.20211381