TIM3+ TRBV11-2 T cells and IFNγ signature in patrolling monocytes and CD16+ NK cells delineate MIS-C-Reference-Cited by-同舟云学术

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

Published:2021-12-16 Issue:2 Volume:219 Page:
ISSN:0022-1007
Container-title:Journal of Experimental Medicine
language:en
Short-container-title:

Author:

Hoste Levi¹²^ORCID,Roels Lisa¹²^ORCID,Naesens Leslie¹²^ORCID,Bosteels Victor³⁴^ORCID,Vanhee Stijn³⁵^ORCID,Dupont Sam³⁵^ORCID,Bosteels Cedric³⁵^ORCID,Browaeys Robin⁶⁷^ORCID,Vandamme Niels⁶⁷^ORCID,Verstaen Kevin⁶⁷^ORCID,Roels Jana⁶⁷^ORCID,Van Damme Karel F.A.³⁵^ORCID,Maes Bastiaan³⁵^ORCID,De Leeuw Elisabeth³⁵^ORCID,Declercq Jozefien³⁵^ORCID,Aegerter Helena³⁵^ORCID,Seys Leen³⁵^ORCID,Smole Ursula³⁵^ORCID,De Prijck Sofie³⁵^ORCID,Vanheerswynghels Manon³⁵^ORCID,Claes Karlien¹²^ORCID,Debacker Veronique¹²^ORCID,Van Isterdael Gert⁸^ORCID,Backers Lynn⁹¹⁰^ORCID,Claes Kathleen B.M.⁹¹⁰^ORCID,Bastard Paul¹¹¹²¹³^ORCID,Jouanguy Emmanuelle¹¹¹²¹³^ORCID,Zhang Shen-Ying¹¹¹²¹³^ORCID,Mets Gilles¹⁴^ORCID,Dehoorne Joke¹⁵^ORCID,Vandekerckhove Kristof¹⁴^ORCID,Schelstraete Petra²^ORCID,Willems Jef¹⁶^ORCID,Willekens Julie,Schaballie Heidi,Van daele Sabine,Dierickx Laure,David Sara,Dhont Evelyn,Verrijckt Ann,de Jaeger Annick,Beel Emma,Matthijs Inge,Minne Aurélie,Decaestecker Karin,John Jijo,Crijnen Thomas E.M.,Koninckx Muriel,Verbruggen Joery,Nys Goele,Akhnikh Samira,Vanlede Koen,Coppens Annelien,Thijs Joke,Ryckaert Ilse,Covents Annick,Duval Els L.I.M.,Verschelde Ann,De Keyzer Linde,Van Ackere Tine,Verbist Astrid,Daeze Charlotte,Becue Caroline,De Paepe Justine,Keepers Jo,Bruylants Bruno,Kuypers Sabine,Daelemans Siel,van der Werff ten Bosch Jutte,van Berlaer Gerlant,Dreesman Alexandra,Florkin Benoit,Heijmans Catherine,Papadopoulos Jean,Stordeur Patrick¹⁷^ORCID,Janssens Sophie³⁴^ORCID,Beyaert Rudi¹⁸¹⁹^ORCID,Saeys Yvan⁶⁷^ORCID,Casanova Jean-Laurent¹¹¹²¹³²⁰²¹^ORCID,Lambrecht Bart N.³⁵²²^ORCID,Haerynck Filomeen¹²^ORCID,Tavernier Simon J.¹¹⁸¹⁹^ORCID,

Affiliation:

1. 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

2. Department of Internal Medicine and Pediatrics, Division of Pediatric Pulmonology, Infectious Diseases and Inborn Errors of Immunity, Ghent University Hospital, Ghent, Belgium

3. Department of Internal Medicine and Pediatrics, Ghent University Hospital, Ghent, Belgium

4. Center for Inflammation Research, Laboratory for Endoplasmic Reticulum Stress and Inflammation, VIB, Ghent, Belgium

5. Center for Inflammation Research, Laboratory of Immunoregulation and Mucosal Immunology, VIB Center for Inflammation Research, Ghent, Belgium

6. Data Mining and Modeling for Biomedicine, VIB Center for Inflammation Research, Ghent, Belgium

7. Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium

8. VIB Flow Core, VIB Center for Inflammation Research, Ghent, Belgium

9. Center for Medical Genetics, Department of Biomolecular Medicine, Ghent University and Ghent University Hospital, Ghent, Belgium

10. Cancer Research Institute Ghent, Ghent University, Ghent, Belgium

11. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France

12. University of Paris, Imagine Institute, Paris, France

13. St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY

14. Department of Internal Medicine and Pediatrics, Division of Pediatric Cardiology, Ghent University Hospital, Ghent, Belgium

15. Department of Internal Medicine and Pediatrics, Division of Pediatric Rheumatology, Ghent University Hospital, Ghent, Belgium

16. Department of Critical Care, Division of Pediatric Intensive Care, Ghent University Hospital, Ghent, Belgium

17. Belgian National Reference Center for the Complement System, Laboratory of Immunology, LHUB-ULB, Université Libre de Bruxelles, Brussels, Belgium

18. Center for Inflammation Research, Laboratory of Molecular Signal Transduction in Inflammation, VIB, Ghent, Belgium

19. Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium

20. Howard Hughes Medical Institute, New York, NY

21. Pediatric Hematology and Immunology Unit, Necker Hospital for Sick Children, AP-HP, Paris, France

22. Department of Pulmonary Medicine, ErasmusMC, Rotterdam, The Netherlands

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.

Funder

Vlaams Instituut voor Biotechnologie

Ghent University

Fonds Wetenschappelijk Onderzoek

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

Link

https://rupress.org/jem/article-pdf/doi/10.1084/jem.20211381/1427181/jem_20211381.pdf

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