Estrogen receptor 8 activation inhibits colitis by promoting NLRP6-mediated autophagy

文献类型： 外文期刊

第一作者： Fan, Wentao

作者： Fan, Wentao;Ding, Chenchen;Liu, Shuhui;Gao, Xiaona;Gao, Zhangshan;Li, Mengcong;Zhang, Shuo;Miao, Yufan;Yan, Liping;Song, Suquan;Shen, Xiaofei;Fan, Wentao;Ding, Chenchen;Liu, Shuhui;Gao, Xiaona;Gao, Zhangshan;Li, Mengcong;Zhang, Shuo;Miao, Yufan;Yan, Liping;Song, Suquan;Fan, Wentao;Ding, Chenchen;Liu, Shuhui;Gao, Xiaona;De Boevre, Marthe;Gao, Zhangshan;Li, Mengcong;Zhang, Shuo;Miao, Yufan;Guan, Wenxian;Liu, Guangliang;Yan, Liping;De Saeger, Sarah;Song, Suquan;De Boevre, Marthe;De Saeger, Sarah;Liu, Guangliang

作者机构：

期刊名称：CELL REPORTS （ 影响因子：9.995； 五年影响因子：10.99 ）

ISSN： 2211-1247

年卷期： 2022 年 41 卷 2 期

页码：

收录情况： SCI

摘要： Estrogen receptor 8 (ER8) and NOD-like receptor family pyrin domain containing 6 (NLRP6) are highly ex-pressed in intestinal tissues. Loss of ER8 and NLRP6 exacerbate colitis in mouse models; however, the un-derlying mechanisms are incompletely understood. Here, we report that ER8 directly activates the NLRP6 gene expression via binding to estrogen responsive element of Nlrp6 gene promoter. ER8 also physically in-teracts with the NLRP6 nucleotide-binding domain and promotes NLRP6 inflammasome assembly. The ER8-NLRP6 axis then interacts with multiple autophagy-related proteins, including ULK1, BECN1, ATG16L1, LC3B, and p62, and affects the autophagosome biogenesis and autophagic flux. Finally, NLRP6-mediated autophagy suppresses the inflammatory response by promoting the K48-linked poly-ubiquitination of ASC, Casp-1 p20, IL-18, TNF-o, and prohibitin-2. Thus, ER8-NLRP6 direct an anti-inflamma-tory response by promoting autophagy. Our work uncovers an ER8-NLRP6-autophagy pathway as a regula-tory mechanism that maintains intestinal epithelial cell homeostasis and facilitates tissue repair in colitis.

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