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Factors regulating the development and maintenance of these liver-resident NK cells are poorly understood. The aryl hydrocarbon receptor (AhR) is a transcription factor modulated by exogenous and endogenous ligands that is important in the homeostasis of immune cells at barrier sites, such as the skin and gut. In this study, we show that liver-resident NK (NK1.1+CD3\u2212) cells, defined as CD49a+TRAIL+CXCR6+DX5\u2212 cells in the mouse liver, constitutively express AhR. In AhR\u2212\/\u2212 mice, there is a significant reduction in the proportion and absolute number of these cells, which results from a cell-intrinsic dependence on AhR. This deficiency in liver-resident NK cells appears to be the result of higher turnover and increased susceptibility to cytokine-induced cell death. Finally, we show that this deficiency has functional implications in vivo. Upon hapten exposure, AhR\u2212\/\u2212 mice are not able to mount an NK cell memory response to hapten rechallenge. Together, these data demonstrate the requirement of AhR for the maintenance of CD49a+TRAIL+CXCR6+DX5\u2212 liver-resident NK cells and their hapten memory function.<\/jats:p>","DOI":"10.1084\/jem.20151998","type":"journal-article","created":{"date-parts":[[2016,9,26]],"date-time":"2016-09-26T14:13:30Z","timestamp":1474899210000},"page":"2249-2257","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":89,"title":["The aryl hydrocarbon receptor is required for the maintenance of liver-resident natural killer cells"],"prefix":"10.1084","volume":"213","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3870-0574","authenticated-orcid":false,"given":"Luhua H.","family":"Zhang","sequence":"first","affiliation":[{"name":"Division of Head and Neck Surgery, Department of Otolaryngology, Program in Immunology, Stanford Cancer Institute and Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9278-1331","authenticated-orcid":false,"given":"June Ho","family":"Shin","sequence":"additional","affiliation":[{"name":"Division of Head and Neck Surgery, Department of Otolaryngology, Program in Immunology, Stanford Cancer Institute and Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7001-9132","authenticated-orcid":false,"given":"Mikel D.","family":"Haggadone","sequence":"additional","affiliation":[{"name":"Division of Head and Neck Surgery, Department of Otolaryngology, Program in Immunology, Stanford Cancer Institute and Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8393-4196","authenticated-orcid":false,"given":"John B.","family":"Sunwoo","sequence":"additional","affiliation":[{"name":"Division of Head and Neck Surgery, Department of Otolaryngology, Program in Immunology, Stanford Cancer Institute and Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2016,9,26]]},"reference":[{"key":"2023072603053305400_bib1","doi-asserted-by":"publisher","first-page":"282","DOI":"10.3389\/fimmu.2014.00282","article-title":"Beyond NK cells: the expanding universe of innate lymphoid cells","volume":"5","author":"Cella","year":"2014","journal-title":"Front. 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