通过向代谢冗余来选择性抑制致病性Th17细胞
Lin Wu1, Kate E R Hollinshead2, Yuhan Hao3
1The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY, USA; New York Genome Center, New York, NY, USA.
Cell
|July 3, 2020
概括
针对T细胞中的葡萄糖代谢提供了新的治疗途径. 抑制葡萄糖酸盐异构酶 (Gpi1) 选择性地消除有害的Th17细胞,保留有益的细胞,用于治疗自身免疫性疾病.
科学领域:
- 免疫学
- 代谢途径
- 细胞代谢
背景情况:
- 葡萄糖溶解对于T细胞功能至关重要,但对其进行向是具有挑战性的.
- 不完全了解T细胞子集的环境依赖的代谢需求.
- Th17细胞在恒温和自身免疫性疾病中起作用.
研究的目的:
- 研究针对T细胞糖解的治疗潜力.
- 确定特定的糖解酶是否可以被选择性地向.
- 探索致病性Th17细胞的代谢脆弱性.
主要方法:
- 在小鼠模型中进行CRISPR介导的基因向.
- 对Th17细胞群的分析 (静态与炎症).
- 代谢流量分析,包括酸盐通路和线粒体呼吸.
主要成果:
- 针对糖分的CRISPR导致了全球的Th17细胞损失.
- Gpi1 缺陷可以选择性地消除 Th17 炎症细胞 (大脑发育,大肠发育).
- 通过其他代谢途径补偿Gpi1损失的恒常Th17细胞.
结论:
- 针对葡萄糖酸盐异构酶 (Gpi1) 提供针对致病性Th17细胞的选择性策略.
- 利用代谢差异可以为自身免疫性疾病提供有针对性的治疗,并降低毒性.
- 可以利用代谢冗余来选择性向与疾病相关的细胞.
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