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Differential involvement of LUBAC‐mediated linear ubiquitination in intestinal epithelial cells and macrophages during intestinal inflammation by Yusuke Sakamoto; Katsuhiro Sasaki; Mayuki Omatsu; Kensuke Hamada; Yuki Nakanishi; Yoshiro Itatani; Kenji Kawada; Kazutaka Obama; Hiroshi Seno; Kazuhiro Iwai is a Medicine article available to read on EtoBox.
What is Differential involvement of LUBAC‐mediated linear ubiquitination in intestinal epithelial cells and macrophages during intestinal inflammation about?
## Abstract Disruption of the intestinal epithelial barrier and dysregulation of macrophages are major factors contributing to the pathogenesis of inflammatory bowel diseases (IBDs). Activation of NF‐κB and cell death are involved in maintaining intestinal homeostasis in a cell type‐dependent manner. Although both are regulated by linear ubiquitin chain assembly complex (LUBAC)‐mediated linear ubiquitination, the physiological relevance of linear ubiquitination to intestinal inflammation remains unexplored. Here, we used two experimental mouse models of IBD (intraperitoneal LPS and oral dextran sodium sulfate [DSS] administration) to examine the role of linear ubiquitination in intestinal epithelial cells (IECs) and macrophages during intestinal inflammation. We did this by deleting the linear ubiquitination activity of LUBAC specifically from IECs or macrophages. Upon LPS administration, loss of ligase activity in IECs induced mucosal inflammation and augmented IEC death. LPS‐mediated death of LUBAC‐defective IECs was triggered by TNF. IEC death was rescued by an anti‐TNF antibody, and TNF (but not LPS) induced apoptosis of organoids derived from LUBAC‐defective IECs. However, aug
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- Author
- Yusuke Sakamoto; Katsuhiro Sasaki; Mayuki Omatsu; Kensuke Hamada; Yuki Nakanishi; Yoshiro Itatani; Kenji Kawada; Kazutaka Obama; Hiroshi Seno; Kazuhiro Iwai
- Publisher
- Wiley
- Published
- 2022
- Language
- EN
- Field
- Medicine (Health Sciences)