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Here, we explored the metabolic processes unique to these cells. Adaptive CD3\u2212CD56dimCD57+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-\u03b3 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.<\/jats:p>","DOI":"10.1084\/jem.20172168","type":"journal-article","created":{"date-parts":[[2018,7,30]],"date-time":"2018-07-30T10:35:13Z","timestamp":1532946913000},"page":"2379-2395","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":138,"title":["ARID5B regulates metabolic programming in human adaptive NK cells"],"prefix":"10.1084","volume":"215","author":[{"given":"Frank","family":"Cichocki","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Minnesota, Minneapolis, MN 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Ying","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Minnesota, Minneapolis, MN 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1717-3218","authenticated-orcid":true,"given":"Bin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Minnesota, Minneapolis, MN 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Felices","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Minnesota, Minneapolis, MN 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Tesi","sequence":"additional","affiliation":[{"name":"Childhood Cancer Research Unit, Department of Women\u2019s and Children\u2019s Health, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden 2"},{"name":"Clinical Genetics Unit, Department of Molecular Medicine and Surgery, and Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Tuininga","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Minnesota, Minneapolis, MN 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip","family":"Dougherty","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Minnesota, Minneapolis, MN 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Taras","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Minnesota, Minneapolis, MN 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Hinderlie","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Minnesota, Minneapolis, MN 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9608-9841","authenticated-orcid":true,"given":"Bruce R.","family":"Blazar","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Minnesota, Minneapolis, MN 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7783-9934","authenticated-orcid":true,"given":"Yenan T.","family":"Bryceson","sequence":"additional","affiliation":[{"name":"Centre for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden 5"},{"name":"Broegelmann Research Laboratory, Department of Clinical Sciences, University of Bergen, Bergen, Norway 6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0339-4944","authenticated-orcid":true,"given":"Jeffrey S.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Minnesota, Minneapolis, MN 1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2018,7,30]]},"reference":[{"key":"2023072604353488600_bib1","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1038\/ncb2228","article-title":"PKA-dependent regulation of the histone lysine demethylase complex PHF2-ARID5B","volume":"13","author":"Baba","year":"2011","journal-title":"Nat. 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