ATG16L1 orchestrates interleukin-22 signaling in the intestinal epithelium via cGAS–STING | Zendy

Konrad Aden | Zendy; Florian Tran | Zendy; Go Ito | Zendy; Raheleh SheibaniTezerji | Zendy; Simone Lipinski | Zendy; J. W. Kuiper | Zendy; Markus Tschurtschenthaler | Zendy; Svetlana Saveljeva | Zendy; Joya Bhattacharyya | Zendy; Robert Häsler | Zendy; Kareen Bartsch | Zendy; Anne Luzius | Zendy; Marlene Jentzsch | Zendy; Maren FalkPaulsen | Zendy; Stephanie T. Stengel | Zendy; Lina Welz | Zendy; Robin Schwarzer | Zendy; Björn Rabe | Zendy; Winfried Barchet | Zendy; Stefan Krautwald | Zendy; Gunther Hartmann | Zendy; Manolis Pasparakis | Zendy; Richard S. Blumberg | Zendy; Stefan Schreiber | Zendy; Arthur Kaser | Zendy; Philip Rosenstiel | Zendy

AI Assistant Blog Pricing

Home ZAIA Blog

Open Access

ATG16L1 orchestrates interleukin-22 signaling in the intestinal epithelium via cGAS–STING

Author(s) -

Konrad Aden,

Florian Tran,

Go Ito,

Raheleh SheibaniTezerji,

Simone Lipinski,

J. W. Kuiper,

Markus Tschurtschenthaler,

Svetlana Saveljeva,

Joya Bhattacharyya,

Robert Häsler,

Kareen Bartsch,

Anne Luzius,

Marlene Jentzsch,

Maren FalkPaulsen,

Stephanie T. Stengel,

Lina Welz,

Robin Schwarzer,

Björn Rabe,

Winfried Barchet,

Stefan Krautwald,

Gunther Hartmann,

Manolis Pasparakis,

Richard S. Blumberg,

Stefan Schreiber,

Arthur Kaser,

Philip Rosenstiel

Publication year - 2018

Publication title -

the journal of experimental medicine

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 8.483

H-Index - 448

eISSN - 1540-9538

pISSN - 0022-1007

DOI - 10.1084/jem.20171029

Subject(s) - atg16l1 , intestinal epithelium , autophagy , intestinal mucosa , inflammatory bowel disease , microbiology and biotechnology , inflammation , cytokine , biology , proinflammatory cytokine , signal transduction , epithelium , cancer research , immunology , apoptosis , medicine , biochemistry , genetics , disease

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 ΔIEC 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 ΔIEC and Atg16l1 ΔIEC / Xbp1 ΔIEC 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 ΔIEC mice. Our data demonstrate an unexpected role of ATG16L1 in coordinating the outcome of IL-22 signaling in the intestinal epithelium.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.

Having issues? You can contact us here

Accelerating Research