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。
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
Cell Metabolism:《细胞—代谢》,创刊于2005年。隶属于细胞出版社,最新IF:22.415
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