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

Levi Hoste (UGent) , Lisa Roels (UGent) , Leslie Naesens (UGent) , Victor Bosteels (UGent) , Stijn Vanhee (UGent) , Sam Dupont (UGent) , Cedric Bosteels (UGent) , Robin Browaeys (UGent) , Niels Vandamme (UGent) , Kevin Verstaen (UGent) , et al.
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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.
Keywords
MULTISYSTEM INFLAMMATORY SYNDROME, INTERFERON-GAMMA, HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS, BARRIER FUNCTION, SARS-COV-2, SHOCK, COVID-19, CHILDREN, DISEASE, LIPOPOLYSACCHARIDE

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MLA
Hoste, Levi, et al. “TIM3+ TRBV11-2 T Cells and IFNγ Signature in Patrolling Monocytes and CD16+ NK Cells Delineate MIS-C.” JOURNAL OF EXPERIMENTAL MEDICINE, vol. 219, no. 2, 2022, doi:10.1084/jem.20211381.
APA
Hoste, L., Roels, L., Naesens, L., Bosteels, V., Vanhee, S., Dupont, S., … MIS-C Clinicians, [ missing ]. (2022). TIM3+ TRBV11-2 T cells and IFNγ signature in patrolling monocytes and CD16+ NK cells delineate MIS-C. JOURNAL OF EXPERIMENTAL MEDICINE, 219(2). https://doi.org/10.1084/jem.20211381
Chicago author-date
Hoste, Levi, Lisa Roels, Leslie Naesens, Victor Bosteels, Stijn Vanhee, Sam Dupont, Cedric Bosteels, et al. 2022. “TIM3+ TRBV11-2 T Cells and IFNγ Signature in Patrolling Monocytes and CD16+ NK Cells Delineate MIS-C.” JOURNAL OF EXPERIMENTAL MEDICINE 219 (2). https://doi.org/10.1084/jem.20211381.
Chicago author-date (all authors)
Hoste, Levi, Lisa Roels, Leslie Naesens, Victor Bosteels, Stijn Vanhee, Sam Dupont, Cedric Bosteels, Robin Browaeys, Niels Vandamme, Kevin Verstaen, Jana Roels, Karel Van Damme, Bastiaan Maes, Elisabeth De Leeuw, Jozefien Declercq, Helena Catharine Aegerter, Leen Seys, Ursula Smole, Sofie De Prijck, Manon Vanheerswynghels, Karlien Claes, Veronique Debacker, Gert Van Isterdael, Lynn Backers, Kathleen Claes, Paul Bastard, Emmanuelle Jouanguy, Shen-Ying Zhang, Gilles Mets, Joke Dehoorne, Kristof Vandekerckhove, Petra Schelstraete, Jef Willems, Patrick Stordeur, Sophie Janssens, Rudi Beyaert, Yvan Saeys, Jean-Laurent Casanova, Bart Lambrecht, Filomeen Haerynck, Simon Tavernier, Heidi Schaballie, and [ missing ] MIS-C Clinicians. 2022. “TIM3+ TRBV11-2 T Cells and IFNγ Signature in Patrolling Monocytes and CD16+ NK Cells Delineate MIS-C.” JOURNAL OF EXPERIMENTAL MEDICINE 219 (2). doi:10.1084/jem.20211381.
Vancouver
1.
Hoste L, Roels L, Naesens L, Bosteels V, Vanhee S, Dupont S, et al. TIM3+ TRBV11-2 T cells and IFNγ signature in patrolling monocytes and CD16+ NK cells delineate MIS-C. JOURNAL OF EXPERIMENTAL MEDICINE. 2022;219(2).
IEEE
[1]
L. Hoste et al., “TIM3+ TRBV11-2 T cells and IFNγ signature in patrolling monocytes and CD16+ NK cells delineate MIS-C,” JOURNAL OF EXPERIMENTAL MEDICINE, vol. 219, no. 2, 2022.
@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://dx.doi.org/10.1084/jem.20211381}},
  volume       = {{219}},
  year         = {{2022}},
}

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