ARID5B regulates metabolic programming in human adaptive NK cells.

The Journal of experimental medicine (2018-08-01)
Frank Cichocki, Cheng-Ying Wu, Bin Zhang, Martin Felices, Bianca Tesi, Katie Tuininga, Phillip Dougherty, Emily Taras, Peter Hinderlie, Bruce R Blazar, Yenan T Bryceson, Jeffrey S Miller

Natural killer (NK) cells with adaptive immunological properties expand and persist in response to human cytomegalovirus. Here, we explored the metabolic processes unique to these cells. Adaptive CD3-CD56dimCD57+NKG2C+ NK cells exhibited metabolic hallmarks of lymphocyte memory, including increased oxidative mitochondrial respiration, mitochondrial membrane potential, and spare respiratory capacity. Mechanistically, we found that a short isoform of the chromatin-modifying transcriptional regulator, AT-rich interaction domain 5B (ARID5B), was selectively induced through DNA hypomethylation in adaptive NK cells. Knockdown and overexpression studies demonstrated that ARID5B played a direct role in promoting mitochondrial membrane potential, expression of genes encoding electron transport chain components, oxidative metabolism, survival, and IFN-γ production. Collectively, our data demonstrate that ARID5B is a key regulator of metabolism in human adaptive NK cells, which, if targeted, may be of therapeutic value.

Product Number
Product Description

Triton X-100, laboratory grade
MISSION® esiRNA, targeting human UQCRB
2-Deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose, ≥97% (HPLC)
MISSION® esiRNA, targeting human ARID5B