| First Author | Aden K | Year | 2018 |
| Journal | J Exp Med | Volume | 215 |
| Issue | 11 | Pages | 2868-2886 |
| PubMed ID | 30254094 | Mgi Jnum | J:269933 |
| Mgi Id | MGI:6273053 | Doi | 10.1084/jem.20171029 |
| Citation | Aden K, et al. (2018) ATG16L1 orchestrates interleukin-22 signaling in the intestinal epithelium via cGAS-STING. J Exp Med 215(11):2868-2886 |
| abstractText | A coding variant of the inflammatory bowel disease (IBD) risk gene ATG16L1 has been associated with defective autophagy and deregulation of endoplasmic reticulum (ER) function. IL-22 is a barrier protective cytokine by inducing regeneration and antimicrobial responses in the intestinal mucosa. We show that ATG16L1 critically orchestrates IL-22 signaling in the intestinal epithelium. IL-22 stimulation physiologically leads to transient ER stress and subsequent activation of STING-dependent type I interferon (IFN-I) signaling, which is augmented in Atg16l1 (DeltaIEC) intestinal organoids. IFN-I signals amplify epithelial TNF production downstream of IL-22 and contribute to necroptotic cell death. In vivo, IL-22 treatment in Atg16l1 (DeltaIEC) and Atg16l1 (DeltaIEC)/Xbp1 (DeltaIEC) mice potentiates endogenous ileal inflammation and causes widespread necroptotic epithelial cell death. Therapeutic blockade of IFN-I signaling ameliorates IL-22-induced ileal inflammation in Atg16l1 (DeltaIEC) mice. Our data demonstrate an unexpected role of ATG16L1 in coordinating the outcome of IL-22 signaling in the intestinal epithelium. |
