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10.1084/jem.20211381

http://scihub22266oqcxt.onion/10.1084/jem.20211381
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34914824!8685281!34914824
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suck abstract from ncbi


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pmid34914824      J+Exp+Med 2022 ; 219 (2): ä
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  • TIM3+ TRBV11-2 T cells and IFNgamma signature in patrolling monocytes and CD16+ NK cells delineate MIS-C #MMPMID34914824
  • Hoste L; Roels L; Naesens L; Bosteels V; Vanhee S; Dupont S; Bosteels C; Browaeys R; Vandamme N; Verstaen K; Roels J; Van Damme KFA; Maes B; De Leeuw E; Declercq J; Aegerter H; Seys L; Smole U; De Prijck S; Vanheerswynghels M; Claes K; Debacker V; Van Isterdael G; Backers L; Claes KBM; Bastard P; Jouanguy E; Zhang SY; Mets G; Dehoorne J; Vandekerckhove K; Schelstraete P; Willems J; Stordeur P; Janssens S; Beyaert R; Saeys Y; Casanova JL; Lambrecht BN; Haerynck F; Tavernier SJ
  • J Exp Med 2022[Feb]; 219 (2): ä PMID34914824show ga
  • 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 IFNgamma and not type I interferon. Persistence of patrolling monocytes differentiates MIS-C from severe COVID-19, which is dominated by HLA-DRlo classical monocytes. IFNgamma 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 TCRbeta repertoire enriched for TRBV11-2 and a superantigenic signature in TIM3+/CD38+/HLA-DR+ T cells. Using NicheNet, we confirm IFNgamma as a central cytokine in the communication between TIM3+/CD38+/HLA-DR+ T cells, CD16+ NK cells, and patrolling monocytes. Normalization of IFNgamma, loss of TIM3, quiescence of CD16+ NK cells, and contraction of patrolling monocytes upon clinical resolution highlight their potential role in MIS-C immunopathogenesis.
  • |Adolescent[MESH]
  • |Alveolar Epithelial Cells/pathology[MESH]
  • |B-Lymphocytes/immunology[MESH]
  • |Blood Vessels/pathology[MESH]
  • |COVID-19/*complications/immunology/pathology[MESH]
  • |Cell Proliferation[MESH]
  • |Child[MESH]
  • |Cohort Studies[MESH]
  • |Complement Activation[MESH]
  • |Cytokines/metabolism[MESH]
  • |Enterocytes/pathology[MESH]
  • |Female[MESH]
  • |Hepatitis A Virus Cellular Receptor 2/*metabolism[MESH]
  • |Humans[MESH]
  • |Immunity, Humoral[MESH]
  • |Inflammation/pathology[MESH]
  • |Interferon Type I/metabolism[MESH]
  • |Interferon-gamma/*metabolism[MESH]
  • |Interleukin-15/metabolism[MESH]
  • |Killer Cells, Natural/*immunology[MESH]
  • |Lymphocyte Activation/immunology[MESH]
  • |Male[MESH]
  • |Monocytes/*metabolism[MESH]
  • |Receptors, Antigen, T-Cell/metabolism[MESH]
  • |Receptors, IgG/*metabolism[MESH]
  • |SARS-CoV-2/immunology[MESH]
  • |Superantigens/metabolism[MESH]
  • |Systemic Inflammatory Response Syndrome/*immunology/pathology[MESH]


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