Last but not least thanks to everyone involved, starting from the @Lo_Zanzi, amazing mentor, the once again amazing @BennieSposito, the first postdoc of the @AB_Lab_CIML Julien Mambu, Philippe Naquet and Franck Galland @CIML_Immunology, @scott_snapper, Jay Thiagarajah
Using ZBP1 KO organoids and shRNA KD of GSDMC we could define that both are required fo IFN-λ induced lethality. Amazingly both GSDMC, ZBP1 and CASP-8 as well as Interferon responsive genes are upregulated in #IBD patients, and GSDMC levels correlate with #IFN responses!
Here's the first pre-print of the @AB_Lab_CIML, joint with @Lo_Zanzi lab. #IFNs are awesome but they can have a dark side. We show tath IFN-λ can delay tissue restitution in the gut by favoring epithelial cell death by #pyroptosis. @CIML_Immunology#IBD https://t.co/WwVlBK7rnw
Mechanistic studies in intestinal organoids recapitulated in vivo observations on gut epithelial cells showing that IFN-λ induces the upregulation of ZBP1, the activation of CASP-8 and the cleavage of the pore forming #gasdermin GDMC culminating in pyroptotic cell death.
We show that IFN-λ administration to mice recovering from colitis or radiation damage severely delays tissue restitution. Blocking endogenous IFN-λ on the other hand favors tissue restitution. IFN-λ in mice diminishes the number of proliferating intestinal stem cells.
Happy to share our paper analyzing the landscape of #IFNs and #IFN responses in the respiratory tract of #COVID19 patients. IFNs in the upper airways drive mild disease while high IFNs in the lower airways correlate with severe symptoms. https://t.co/fMd3uU8Hkv