安普克
细胞生物学
化学
碳水化合物代谢
脂质代谢
AMP活化蛋白激酶
生物
磷酸化
生物化学
蛋白激酶A
作者
Eline C. Brombacher,Thiago A. Patente,Alwin J. van der Ham,Tijmen J.A. Moll,Frank Otto,Frans W. Verheijen,Esther A. Zaal,Arnoud H. de Ru,Rayman T.N. Tjokrodirijo,Celia R. Berkers,Peter A. van Veelen,Bruno Guigas,Bart Everts
标识
DOI:10.1083/jcb.202401024
摘要
Dendritic cell (DC) activation and function are underpinned by profound changes in cellular metabolism. Several studies indicate that the ability of DCs to promote tolerance is dependent on catabolic metabolism. Yet the contribution of AMP-activated kinase (AMPK), a central energy sensor promoting catabolism, to DC tolerogenicity remains unknown. Here, we show that AMPK activation renders human monocyte-derived DCs tolerogenic as evidenced by an enhanced ability to drive differentiation of regulatory T cells, a process dependent on increased RALDH activity. This is accompanied by several metabolic changes, including increased breakdown of glycerophospholipids, enhanced mitochondrial fission–dependent fatty acid oxidation, and upregulated glucose catabolism. This metabolic rewiring is functionally important as we found interference with these metabolic processes to reduce to various degrees AMPK-induced RALDH activity as well as the tolerogenic capacity of moDCs. Altogether, our findings reveal a key role for AMPK signaling in shaping DC tolerogenicity and suggest AMPK as a target to direct DC-driven tolerogenic responses in therapeutic settings.
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