Notch1-CD22-Dependent Immune Dysregulation in the SARS-CoV2-Associated Multisystem Inflammatory Syndrome in Children.
Res Sq
; 2022 Apr 11.
Artigo
em Inglês
| MEDLINE | ID: covidwho-1786451
ABSTRACT
Multisystem inflammatory syndrome in children (MIS-C) evolves in some pediatric patients following acute infection with SARS-CoV-2 by hitherto unknown mechanisms. Whereas acute-COVID-19 severity and outcome were previously correlated with Notch4 expression on regulatory T (Treg) cells, here we show that the Treg cells in MIS-C are destabilized in association with increased Notch1 expression. Genetic analysis revealed that MIS-C patients were enriched in rare deleterious variant impacting inflammation and autoimmunity pathways, including dominant negative mutations in the Notch1 regulators NUMB and NUMBL . Notch1 signaling in Treg cells induced CD22, leading to their destabilization in an mTORC1 dependent manner and to the promotion of systemic inflammation. These results establish a Notch1-CD22 signaling axis that disrupts Treg cell function in MIS-C and point to distinct immune checkpoints controlled by individual Treg cell Notch receptors that shape the inflammatory outcome in SARS-CoV-2 infection.
Texto completo:
Disponível
Coleções:
Bases de dados internacionais
Base de dados:
MEDLINE
Tipo de estudo:
Estudo experimental
/
Estudo prognóstico
Tópicos:
Variantes
Idioma:
Inglês
Ano de publicação:
2022
Tipo de documento:
Artigo
Similares
MEDLINE
...
LILACS
LIS