通过Aconitate:门德尔随机化和实验证据,M-CSF可以预防性结肠炎
Yuan Zhang1,2, Longbin Huang3, Ningning Yue3
1Department of Gastroenterology, Shenzhen People's Hospital (the Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, People's Republic of China.
巨菌群刺激因子 (M-CSF) 通过增加酸盐水平来保护性结肠炎 (UC),该酸盐水平转化为抗炎代谢物伊塔康酸盐. 这一途径减少了UC风险和炎症.
科学领域:
- 免疫学 免疫学 免疫学
- 胃肠病学 胃肠病学
- 代谢学 代谢学 代谢学
背景情况:
- 细胞因子与性结肠炎 (UC) 病原发生有关.
- 代谢物介导的细胞因子在UC中的作用尚不清楚.
研究的目的:
- 通过使用孟德尔随机化 (MR) 研究细胞因子对UC发育的代谢物中介作用.
- 探索巨菌群刺激因子 (M-CSF) 在UC中的治疗潜力.
主要方法:
- 使用GWAS数据对91种细胞因子,1400种代谢物和178,689个UC病例进行双样本孟德尔随机化 (MR) 分析.
- 两个步骤的MR评估调解效应.
- 德克斯硫酸 (DSS) 诱导的大肠炎小鼠模型用于体内验证.
主要成果:
- M-CSF与酸盐正相关;高酸盐水平与UC风险降低有关.
- M-CSF显示与UC发病的反相关性.
- 甲基调解了M-CSF对UC的保护作用.
- 在小鼠中,M-CSF治疗改善了结肠炎症状,并通过增加akonitate/itaconate和减少M1巨细胞减少了炎症.
结论:
- 在UC中,M-CSF表现出抗炎性质,可能是通过aconitate-itaconate路径调节.
- M-CSF代表了性结肠炎的一个有前途的治疗标.
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