ACC1是Treg稳定性和免疫耐受性的双重代谢-表观遗传调节剂
Philipp Stüve1, Gloria J Godoy2, Fernando N Ferreyra3
1Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, Germany; A Joint Venture Between the Hannover Medical School (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover 30625, Germany; Leibniz Institute for Immunotherapy, Regensburg, Germany; Institute of Medical Microbiology and Hygiene, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz 55122, Germany.
抑制乙-CoA碳酸酶1 (ACC1) 增强了调控性T细胞 (Treg) 的稳定性和功能. 这种代谢检查点通过促进Treg分化和表观遗传修饰来促进免疫耐受性和控制炎症.
科学领域:
- 免疫学 免疫学 免疫学
- 代谢途径 代谢途径
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 调节性T细胞 (Tregs) 对于免疫平衡和预防自身免疫是至关重要的.
- 特雷格稳定性受到表观遗传修饰的调节,包括基因素和蛋白质乙化.
- 对于Treg分化和功能的代谢要求尚未完全理解.
研究的目的:
- 为了研究乙-CoA碳酸酶1 (ACC1) 在Treg分化,稳定性和功能中的作用.
- 为了确定ACC1抑制是否影响Treg介导的免疫耐受性和炎症控制.
主要方法:
- 利用了T细胞特异性ACC1淘汰小鼠和药理学ACC1抑制.
- 评估了Treg分化和稳定性在体外和体内.
- 在炎症性疾病的收养转移模型中评估Treg功能.
主要成果:
- 抑制或删除ACC1增加了乙-CoA,增强了基因组和蛋白质乙化.
- 在炎症条件下观察到持续的FoxP3转录.
- 抑制ACC1促进了Treg分化,稳定性,并改善了抑制Th1/Th17驱动的炎症.
结论:
- ACC1充当了调节Treg生物学的代谢检查点.
- 抑制ACC1增强了Treg分化和长期稳定性.
- 抑制ACC1代表了对免疫耐受性和炎症性疾病的潜在治疗策略.
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