Porcine GWAS identifies ACOT11 as regulator for macrophage IL-1β maturation via IFNGR2 palmitoylation

文献类型： 外文期刊

第一作者： Zhang, Meimei

作者： Zhang, Meimei;Liu, Shaojuan;Wu, Zebiao;Wang, Chuanlong;Zhang, Hangchao;Yang, Jie;Guo, Chunhe;Dai, Manman;Wang, Xiaofan;Ren, Wenkai;Liu, Shaojuan;Liu, Shaojuan

作者机构：

关键词： ACOT11; macrophage; fatty acid; IFNGR2; palmitoylation

期刊名称：SCIENCE CHINA-LIFE SCIENCES （ 影响因子：9.5； 五年影响因子：8.1 ）

ISSN： 1674-7305

年卷期： 2025 年

页码：

收录情况： SCI

摘要： Fatty acid metabolism mediates macrophage function; however, the underlying mechanism by which fatty acid metabolism regulates macrophage interleukin (IL)-1 beta production remains to be uncovered. Here, we used genome-wide association studies (GWAS) to identify several porcine serum IL-1 beta-related genes, such as the fatty acid metabolizing enzyme acyl-CoA thioesterase 11 (ACOT11). We then demonstrated that inflammatory macrophages have low expression of ACOT11, and ACOT11 overexpression inhibits IL-1 beta maturation from inflammatory macrophages. Mechanistically, ACOT11 promotes intracellular fatty acids accumulation, including eicosatetraenoic acid (EA) and stearic acid (SA), which inhibit activation of the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling through palmitoylation of interferon (IFN)-gamma receptor (IFNGR) 2 at C261site. Furthermore, we also found that EA attenuates lipopolysaccharide (LPS)-induced sepsis in mice. Collectively, our findings reveal a mechanism involving ACOT11-mediated post-translational modification that regulates macrophage function and provide a promising therapeutic target for the treatment of inflammatory diseases associated with macrophages.

分类号：

  • 相关文献
作者其他论文 更多>>

微信小程序