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.
【초록키워드】 Monocytes, severe COVID-19, T cells, SARS-COV-2 infection, pediatric, children, NK cell, NK cells, cytokine, immunopathology, type I interferon, MIS-C, Endotheliitis, Cytokine release syndrome, monocyte, Adults, Immunopathogenesis, TCR, expression, epithelial, granzyme B, Inflammatory, Injury, TRBV11-2, Vascular, IFNγ, syndrome, normalization, classical monocytes, instances, CD16+, highlight, characterized, reveal, IFNγ level, skewed, 【제목키워드】 NK cell, MIS-C, monocyte, T cell, TRBV11-2, IFNγ, CD16+,