@article{8727582,
  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 IFN gamma and not type I interferon. Persistence of patrolling monocytes differentiates MIS-C from severe COVID-19, which is dominated by HLA-DRlo classical monocytes. IFN gamma 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 TCR beta repertoire enriched for TRBV11-2 and a superantigenic signature in TIM3(+)/CD38(+)/HLA-DR+ T cells. Using NicheNet, we confirm IFN gamma as a central cytokine in the communication between TIM3(+)/CD38(+)/HLA-DR+ T cells, CD16(+) NK cells, and patrolling monocytes. Normalization of IFN gamma, loss of TIM3, quiescence of CD16(+) NK cells, and contraction of patrolling monocytes upon clinical resolution highlight their potential role in MIS-C immunopathogenesis.

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 IFN gamma-mediated interactions between T cells, monocytes, and NK cells reside at the heart of the disease.}},
  articleno    = {{e20211381}},
  author       = {{Hoste, Levi and Roels, Lisa and Naesens, Leslie and Bosteels, Victor and Vanhee, Stijn and Dupont, Sam and Bosteels, Cedric and Browaeys, Robin and Vandamme, Niels and Verstaen, Kevin and Roels, Jana and Van Damme, Karel and Maes, Bastiaan and De Leeuw, Elisabeth and Declercq, Jozefien and Aegerter, Helena Catharine and Seys, Leen and Smole, Ursula and De Prijck, Sofie and Vanheerswynghels, Manon and Claes, Karlien and Debacker, Veronique and Van Isterdael, Gert and Backers, Lynn and Claes, Kathleen and Bastard, Paul and Jouanguy, Emmanuelle and Zhang, Shen-Ying and Mets, Gilles and Dehoorne, Joke and Vandekerckhove, Kristof and Schelstraete, Petra and Willems, Jef and Stordeur, Patrick and Janssens, Sophie and Beyaert, Rudi and Saeys, Yvan and Casanova, Jean-Laurent and Lambrecht, Bart and Haerynck, Filomeen and Tavernier, Simon and Schaballie, Heidi and MIS-C Clinicians, [ missing ]}},
  issn         = {{0022-1007}},
  journal      = {{JOURNAL OF EXPERIMENTAL MEDICINE}},
  keywords     = {{MULTISYSTEM INFLAMMATORY SYNDROME,INTERFERON-GAMMA,HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS,BARRIER FUNCTION,SARS-COV-2,SHOCK,COVID-19,CHILDREN,DISEASE,LIPOPOLYSACCHARIDE}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{27}},
  title        = {{TIM3+ TRBV11-2 T cells and IFNγ signature in patrolling monocytes and CD16+ NK cells delineate MIS-C}},
  url          = {{http://doi.org/10.1084/jem.20211381}},
  volume       = {{219}},
  year         = {{2022}},
}

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