AI Article Synopsis
- Multisystem inflammatory syndrome in children (MIS-C) may develop in some kids after SARS-CoV-2 infection due to reasons that are not fully understood.
- The study found that Treg cells in MIS-C patients are destabilized due to increased Notch1 expression, contrasting previous findings with Notch4 in acute COVID-19.
- Genetic analysis showed that MIS-C patients have rare mutations affecting inflammation pathways, highlighting a Notch1-CD22 signaling mechanism that disrupts Treg function and contributes to systemic inflammation.*
Article 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 and . 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.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9016654 | PMC |
| http://dx.doi.org/10.21203/rs.3.rs-1054453/v1 | DOI Listing |
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