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记忆T细胞通过重塑乙酸盐吸收实现炎症平衡
作者:小柯机器人 发布时间:2020/8/3 14:57:34

瑞士巴塞尔大学Christoph Hess、Maria L. Balmer等研究人员合作发现,记忆CD8+T细胞通过重编程感染部位的乙酸盐来实现促炎和抗炎活性的平衡。这一研究成果于2020年7月31日在线发表在《细胞—代谢》上。

研究人员表明在感染部位,乙酸盐浓度很高,但是记忆CD8+T细胞关闭了乙酸盐同化酶ACSS1和ACSS2。因此,乙酸酯被排除在细胞代谢途径之外,从而具有不同的作用,即(1)直接激活谷氨酰胺酶,进而增强谷氨酰胺分解、细胞呼吸和存活,以及(2)抑制TCR触发的钙流,进而抑制细胞激活和效应细胞功能。
 
在体内,感染部位的高乙酸盐含量可提高病原体清除率,同时减少免疫病理。这表明,在免疫反应的不同阶段,相同的代谢产物乙酸盐会在同一细胞类型内诱导不同的免疫代谢程序。
 
据了解,全身感染后血清乙酸盐增加。急性乙酸盐吸收增加了记忆CD8+T细胞产生IFN-γ的能力。乙酸盐是否在病原体再次遭遇期间调节记忆CD8+T细胞的代谢和功能尚待探讨。
 
附:英文原文

Title: Memory CD8+ T Cells Balance Pro- and Anti-inflammatory Activity by Reprogramming Cellular Acetate Handling at Sites of Infection

Author: Maria L. Balmer, Eric H. Ma, Andrew Thompson, Raja Epple, Gunhild Unterstab, Jonas Ltscher, Philippe Dehio, Christian M. Schürch, Jan D. Warncke, Galle Perrin, Anne-Kathrin Woischnig, Jasmin Grhlert, Jordan Lliger, Nadine Assmann, Glenn R. Bantug, Olivier P. Schren, Nina Khanna, Adrian Egli, Lukas Bubendorf, Katharina Rentsch, Siegfried Hapfelmeier, Russell G. Jones, Christoph Hess

Issue&Volume: 2020-07-31

Abstract: Serum acetate increases upon systemic infection. Acutely, assimilation of acetateexpands the capacity of memory CD8+ T cells to produce IFN-γ. Whether acetate modulates memory CD8+ T cell metabolism and function during pathogen re-encounter remains unexplored. Herewe show that at sites of infection, high acetate concentrations are being reached,yet memory CD8+ T cells shut down the acetate assimilating enzymes ACSS1 and ACSS2. Acetate, beingthus largely excluded from incorporation into cellular metabolic pathways, now haddifferent effects, namely (1) directly activating glutaminase, thereby augmentingglutaminolysis, cellular respiration, and survival, and (2) suppressing TCR-triggeredcalcium flux, and consequently cell activation and effector cell function. In vivo, high acetate abundance at sites of infection improved pathogen clearance while reducingimmunopathology. This indicates that, during different stages of the immune response,the same metabolite—acetate—induces distinct immunometabolic programs within the samecell type.

DOI: 10.1016/j.cmet.2020.07.004

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30362-4

期刊信息

Cell Metabolism:《细胞—代谢》,创刊于2005年。隶属于细胞出版社,最新IF:22.415
官方网址:https://www.cell.com/cell-metabolism/home
投稿链接:https://www.editorialmanager.com/cell-metabolism/default.aspx