Gasdermin-E-mediated pyroptosis participates in the pathogenesis of Crohn’s disease by promoting intestinal inflammation

• DOI: 10.1016/j.celrep.2021.109265
• Publication Date: 2021-06-15T14:48:44Z
• Authors: Gao Tan; Chongyang Huang; Jiaye Chen; Bingxia Chen; Fachao Zhi
• Keywords: Male; Pore Forming Cytotoxic Proteins; 0301 basic medicine; QH301-705.5; Severity of Illness Index; Mice; 03 medical and health sciences; Crohn Disease; Pyroptosis; Animals; Humans; Biology (General); HMGB1 Protein; Intestinal Mucosa; Inflammation; pyroptosis; gasdermin E; intestinal epithelial cell; Epithelial Cells; Colitis; 16. Peace & justice; Hematopoiesis; 3. Good health; Intestines; Mice, Inbred C57BL; Crohn's disease; Trinitrobenzenesulfonic Acid

Crohn's disease (CD) is a kind of refractory intestinal inflammatory diseases. Pyroptosis was recently identified as a gasdermin-mediated proinflammatory cell death. However, it is unclear whether gasdermin-mediated pyroptosis participates in the pathogenesis of CD. Here, we show that the pyroptosis-inducing fragment GSDME N-terminal is obviously detected in the inflamed colonic mucosa but not in the uninflamed mucosa of patients with CD, suggesting that GSDME-mediated pyroptosis may be correlated with intestinal mucosal inflammation in CD. To investigate the role of GSDME in colitis development, Gsdme-/- mice and wild-type (WT) littermate controls were treated with 2,4,6-trinitrobenzenesulfonic acid (TNBS) to induce colitis. We found that Gsdme-/- mice exhibit less-severe intestinal inflammation than WT controls do. Furthermore, our results indicate that GSDME-mediated epithelial-cell pyroptosis induces intestinal inflammation through the release of proinflammatory intracellular contents. In summary, we show that GSDME participates in the pathogenesis of CD through GSDME-mediated pyroptosis to release proinflammatory cytokines.