Published 2022
| Version v1
Publication
Notch1-CD22-Dependent Immune Dysregulation in the SARS-CoV2-Associated Multisystem Inflammatory Syndrome in Children
Creators
- Chatila, Talal A
- Benamar, Mehdi
- Chen, Qian
- Chou, Janet
- Julé, Amelie
- Boudra, Rafik
- Contini, Paola
- Crestani, Elena
- Wang, Muyun
- Fong, Jason
- Lai, Peggy
- Rockwitz, Shira
- Lee, Pui
- Chan, Tsz Man Fion
- Altun, Ekin Zeynep
- Kepenekli, Eda
- Karakoc-Aydiner, Elif
- Ozen, Ahmet
- Boran, Perran
- Aygun, Fatih
- Onal, Pinar
- Sakalli, Ayse Ayzit Kilinc
- Cokugras, Haluk
- Gelmez, Metin
- Öktelik, Fatma
- Cetin, Esin Aktaş
- Zhong, Yuelin
- Taylor, Maria
- Irby, Katherine
- Halasa, Natasha
- Signa, Sara
- Prigione, Ignazia
- Gattorno, Marco
- Cotugno, Nicola
- Amodio, Donato
- Geha, Raif
- Son, Mary Beth
- Newburger, Jane
- Agrawal, Pankaj
- Volpi, Stefano
- Palma, Paolo
- Kiykim, Ayca
- Randolph, Adrienne
- Deniz, Gunnur
- Baris, Safa
- De Palma, Raffaele
- Schmitz-Abe, Klaus
- Charbonnier, Louis-Marie
- Henderson, Lauren
Contributors
Others:
- Chatila, Talal A
- Benamar, Mehdi
- Chen, Qian
- Chou, Janet
- Julé, Amelie
- Boudra, Rafik
- Contini, Paola
- Crestani, Elena
- Wang, Muyun
- Fong, Jason
- Lai, Peggy
- Rockwitz, Shira
- Lee, Pui
- Chan, Tsz Man Fion
- Altun, Ekin Zeynep
- Kepenekli, Eda
- Karakoc-Aydiner, Elif
- Ozen, Ahmet
- Boran, Perran
- Aygun, Fatih
- Onal, Pinar
- Sakalli, Ayse Ayzit Kilinc
- Cokugras, Haluk
- Gelmez, Metin
- Öktelik, Fatma
- Cetin, Esin Aktaş
- Zhong, Yuelin
- Taylor, Maria
- Irby, Katherine
- Halasa, Natasha
- Signa, Sara
- Prigione, Ignazia
- Gattorno, Marco
- Cotugno, Nicola
- Amodio, Donato
- Geha, Raif
- Son, Mary Beth
- Newburger, Jane
- Agrawal, Pankaj
- Volpi, Stefano
- Palma, Paolo
- Kiykim, Ayca
- Randolph, Adrienne
- Deniz, Gunnur
- Baris, Safa
- De Palma, Raffaele
- Schmitz-Abe, Klau
- Charbonnier, Louis-Marie
- Henderson, Lauren
Description
: 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.
Additional details
Identifiers
- URL
- https://hdl.handle.net/11567/1134716
- URN
- urn:oai:iris.unige.it:11567/1134716
Origin repository
- Origin repository
- UNIGE