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Beckmann, Noam D.;
Comella, Phillip H.;
Cheng, Esther;
Lepow, Lauren;
Beckmann, Aviva G.;
Tyler, Scott R.;
Mouskas, Konstantinos;
Simons, Nicole W.;
Hoffman, Gabriel E.;
Francoeur, Nancy J.;
Del Valle, Diane Marie;
Kang, Gurpawan;
Do, Anh;
Moya, Emily;
Wilkins, Lillian;
Le Berichel, Jessica;
Chang, Christie;
Marvin, Robert;
Calorossi, Sharlene;
Lansky, Alona;
Walker, Laura;
Yi, Nancy;
Yu, Alex;
Chung, Jonathan;
[...]
Downregulation of exhausted cytotoxic T cells in gene expression networks of multisystem inflammatory syndrome in children
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- Medientyp: E-Artikel
- Titel: Downregulation of exhausted cytotoxic T cells in gene expression networks of multisystem inflammatory syndrome in children
- Beteiligte: Beckmann, Noam D.; Comella, Phillip H.; Cheng, Esther; Lepow, Lauren; Beckmann, Aviva G.; Tyler, Scott R.; Mouskas, Konstantinos; Simons, Nicole W.; Hoffman, Gabriel E.; Francoeur, Nancy J.; Del Valle, Diane Marie; Kang, Gurpawan; Do, Anh; Moya, Emily; Wilkins, Lillian; Le Berichel, Jessica; Chang, Christie; Marvin, Robert; Calorossi, Sharlene; Lansky, Alona; Walker, Laura; Yi, Nancy; Yu, Alex; Chung, Jonathan; [...]
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Erschienen:
Springer Science and Business Media LLC, 2021
- Erschienen in: Nature Communications
- Sprache: Englisch
- DOI: 10.1038/s41467-021-24981-1
- ISSN: 2041-1723
- Entstehung:
- Anmerkungen:
- Beschreibung: <jats:title>Abstract</jats:title><jats:p>Multisystem inflammatory syndrome in children (MIS-C) presents with fever, inflammation and pathology of multiple organs in individuals under 21 years of age in the weeks following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although an autoimmune pathogenesis has been proposed, the genes, pathways and cell types causal to this new disease remain unknown. Here we perform RNA sequencing of blood from patients with MIS-C and controls to find disease-associated genes clustered in a co-expression module annotated to CD56<jats:sup>dim</jats:sup>CD57<jats:sup>+</jats:sup> natural killer (NK) cells and exhausted CD8<jats:sup>+</jats:sup> T cells. A similar transcriptome signature is replicated in an independent cohort of Kawasaki disease (KD), the related condition after which MIS-C was initially named. Probing a probabilistic causal network previously constructed from over 1,000 blood transcriptomes both validates the structure of this module and reveals nine key regulators, including TBX21, a central coordinator of exhausted CD8<jats:sup>+</jats:sup> T cell differentiation. Together, this unbiased, transcriptome-wide survey implicates downregulation of NK cells and cytotoxic T cell exhaustion in the pathogenesis of MIS-C.</jats:p>
- Zugangsstatus: Freier Zugang