ARID5B Regulates Metabolic Programming in Human Adaptive NK Cells

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2018 Aug 1

PMID 30061358

Citations 77

Authors

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

Affiliations

Soon will be listed here.

Abstract

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 CD3CD56CD57NKG2C 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.

Citing Articles

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