• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cell metabolism >Pharmacological Activation of Pyruvate Kinase M2 Inhibits CD4(+) T Cell Pathogenicity and Suppresses Autoimmunity
【24h】

Pharmacological Activation of Pyruvate Kinase M2 Inhibits CD4(+) T Cell Pathogenicity and Suppresses Autoimmunity

机译：丙酮酸激酶M2的药理活化抑制CD4（+）T细胞致病性并抑制自身免疫性

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Pyruvate kinase (PK) catalyzes the conversion of phosphoenolpyruvate to pyruvate during glycolysis. The PK isoform PKM2 has additional roles in regulation of gene transcription and protein phosphorylation. PKM2 has been shown to control macrophage metabolic remodeling in inflammation, but its role in T cell biology is poorly understood. Here, we report PKM2 upregulation, phosphorylation, and nuclear accumulation in murine and human CD4(+) T cells following activation in vitro. Treatment of T cells with TEPP-46, an allosteric activator that induces PKM2 tetramerization and blocks its nuclear translocation, strongly reduces their activation, proliferation, and cytokine production by inhibiting essential signaling pathways and thus preventing the engagement of glycolysis. TEPP-46 limits the development of both T helper 17 (Th17) and Th1 cells in vitro and ameliorates experimental autoimmune encephalomyelitis (EAE) in vivo. Overall, our results suggest that pharmacological targeting of PKM2 may represent a valuable therapeutic approach in T cell-mediated inflammation and autoimmunity.
机译：丙酮酸激酶（PK）催化磷酸溶胶在糖溶解期间磷酸溶胶转化为丙酮酸。 PK同种型PKM2在基因转录和蛋白质磷酸化调节方面具有额外的作用。 PKM2已被证明可以控制炎症中的巨噬细胞代谢重塑，但其在T细胞生物学中的作用很差。在此，在体外激活后，我们在鼠和人CD4（+）T细胞中报告PKM2上调，磷酸化和核积累。用TEPP-46处理T细胞，一种诱导PKM2四聚化并阻断其核易位的变形活化剂，强烈通过抑制必要的信号通路来强调其活化，增殖和细胞因子产生，从而防止糖醇的接合。 TEPP-46限制了体外体外的T辅助17（TH17）和TH1细胞的发展，并在体内改善了实验性自身免疫脑脊髓炎（EAE）。总体而言，我们的研究结果表明PKM2的药理学靶向可以代表T细胞介导的炎症和自身免疫中的有价值的治疗方法。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号