학술논문
TIM3+ TRBV11-2 T cells and IFNγ signature in patrolling monocytes and CD16+ NK cells delineate MIS-C
Document Type
Article
Author
Hoste, Levi; Roels, Lisa; Naesens, Leslie; Bosteels, Victor; Vanhee, Stijn; Dupont, Sam; Bosteels, Cedric; Browaeys, Robin; Vandamme, Niels; Verstaen, Kevin; Roels, Jana; Van Damme, Karel F.A.; Maes, Bastiaan; De Leeuw, Elisabeth; Declercq, Jozefien; Aegerter, Helena; Seys, Leen; Smole, Ursula; De Prijck, Sofie; Vanheerswynghels, Manon; Claes, Karlien; Debacker, Veronique; Van Isterdael, Gert; Backers, Lynn; Claes, Kathleen B.M.; Bastard, Paul; Jouanguy, Emmanuelle; Zhang, Shen-Ying; Mets, Gilles; Dehoorne, Joke; Vandekerckhove, Kristof; Schelstraete, Petra; Willems, Jef; Stordeur, Patrick; Janssens, Sophie; Beyaert, Rudi; Saeys, Yvan; Casanova, Jean-Laurent; Lambrecht, Bart N.; Haerynck, Filomeen; Tavernier, Simon J.
Source
The Journal of Experimental Medicine; February 2022, Vol. 219 Issue: 2 pe20211381-e20211381, 1p
Subject
Language
ISSN
00221007; 15409538
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.