Scholarlink

<p>Fatty acid metabolism mediates macrophage function; however, the underlying mechanism by which fatty acid metabolism regulates macrophage interleukin (IL)-1β production remains to be uncovered. Here, we used genome-wide association studies (GWAS) to identify several porcine serum IL-1β-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-1β 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)-γ 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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 发表日期：

    2025年7月25日

查看全文
  • Meimei Zhang,
  • Shaojuan Liu,
  • Zebiao Wu,
  • Chuanlong Wang,
  • Hangchao Zhang,
  • Jie Yang,
  • Chunhe Guo,
  • Manman Dai,
  • Xiaofan Wang,
  • Wenkai Ren

摘要

Fatty acid metabolism mediates macrophage function; however, the underlying mechanism by which fatty acid metabolism regulates macrophage interleukin (IL)-1β production remains to be uncovered. Here, we used genome-wide association studies (GWAS) to identify several porcine serum IL-1β-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-1β 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)-γ 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.