近日,德国科隆大学Manolis Pasparakis研究团队发现,FADD和Caspase-8通过控制MLKL和GSDMD介导的肠上皮细胞死亡来调节肠道稳态和炎症。该项研究成果于2020年5月1日在线发表在《免疫》杂志上。
Title: FADD and Caspase-8 Regulate Gut Homeostasis and Inflammation by Controlling MLKL- and GSDMD-Mediated Death of Intestinal Epithelial Cells
Author: Robin Schwarzer, Huipeng Jiao, Laurens Wachsmuth, Achim Tresch, Manolis Pasparakis
Issue&Volume: 2020-05-01
Abstract: Pathways controlling intestinal epithelial cell (IEC) death regulate gut immune homeostasisand contribute to the pathogenesis of inflammatory bowel diseases. Here, we show thatcaspase-8 and its adapter FADD act in IECs to regulate intestinal inflammation downstreamof Z-DNA binding protein 1 (ZBP1)- and tumor necrosis factor receptor-1 (TNFR1)-mediatedreceptor interacting protein kinase 1 (RIPK1) and RIPK3 signaling. Mice with IEC-specificFADD or caspase-8 deficiency developed colitis dependent on mixed lineage kinase-like(MLKL)-mediated epithelial cell necroptosis. However, MLKL deficiency fully preventedileitis caused by epithelial caspase-8 ablation, but only partially ameliorated ileitisin mice lacking FADD in IECs. Our genetic studies revealed that caspase-8 and gasdermin-D(GSDMD) were both required for the development of MLKL-independent ileitis in micewith epithelial FADD deficiency. Therefore, FADD prevents intestinal inflammationdownstream of ZBP1 and TNFR1 by inhibiting both MLKL-induced necroptosis and caspase-8-GSDMD-dependentpyroptosis-like death of epithelial cells.
DOI: 10.1016/j.immuni.2020.04.002
Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30160-6
Immunity:《免疫》,创刊于1994年。隶属于细胞出版社,最新if:21.522
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