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纯原体受体P2Y12通过T细胞的基酶2-依赖型糖解来增强自身免疫性肝炎
Wei Zhuang1,2,3, Xiucheng Liu4, Guangyu Liu1
1Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
International journal of biological sciences
|July 27, 2023
概括
纯原体受体P2Y12 (P2RY12) 驱动免疫性肝炎中的T细胞代谢重编程. 抑制P2RY12可减少炎症和T细胞功能障碍,为自身免疫性疾病提供潜在的治疗点.
科学领域:
- 免疫代谢过程中的免疫代谢.
- T细胞生物学T细胞生物学
- 自身免疫性疾病是一种自身免疫性疾病.
背景情况:
- 代谢显著影响免疫细胞功能和自身免疫性疾病.
- 纯原体受体P2Y12 (P2RY12) 在T细胞代谢中的作用正在研究中.
研究的目的:
- 研究P2RY12在T细胞代谢中的作用及其对康卡纳瓦林A (ConA) 诱导的免疫性肝炎的影响.
- 确定P2RY12作为免疫介导性肝病的潜在治疗点.
主要方法:
- 康卡纳瓦林A (ConA) 诱导的免疫性肝炎小鼠模型.
- P2RY12缺乏和药物抑制 (克洛皮多格雷尔,蒂卡格雷勒).
- 蛋白质组学和代谢组学分析,西部抹杀,流细胞计.
主要成果:
- 在ConA诱导的免疫性肝炎中,P2RY12缺乏或抑制降低了炎症媒介和T细胞功能低下.
- P2RY12促进T细胞的新陈代谢重编程,从氧化酸化到通过2 (HK2) 稳定酶稳定酶的糖解.
- 通过激活PI3K/Akt通路,P2RY12防止了HK2的降解,从而抑制了溶酶体的降解.
结论:
- P2RY12是T细胞代谢和免疫性肝炎激活的关键调节者.
- 准P2RY12及其下游效应器HK2为T细胞介导的自身免疫性疾病提供了一个有前途的治疗策略.
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