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During infection, multiple cell types expressed the IL-10 reporter but NK cells were a major early source of this cytokine. These IL-10 reporter+ NK cells expressed high levels of the IL-12 target genes T-bet, KLRG1, and IFN-\u03b3, and IL-12 depletion abrogated reporter expression. However, IL-12 signaling alone was not sufficient to promote NK cell IL-10, and activation of the aryl hydrocarbon receptor (AHR) was also required for maximal IL-10 production. NK cells basally expressed the AHR, relevant chaperone proteins, and the AHR nuclear translocator, which heterodimerizes with the AHR to form a competent transcription factor. In vitro studies revealed that IL-12 stimulation increased NK cell AHR levels, and the AHR and AHR nuclear translocator were required for optimal production of IL-10. Additionally, NK cells isolated from T. gondii\u2013infected Ahr\u2212\/\u2212 mice had impaired expression of IL-10, which was associated with increased resistance to this infection. Taken together, these data identify the AHR as a critical cofactor involved in NK cell production of IL-10.<\/jats:p>","DOI":"10.4049\/jimmunol.1300497","type":"journal-article","created":{"date-parts":[[2014,1,9]],"date-time":"2014-01-09T05:39:45Z","timestamp":1389245985000},"page":"1661-1670","source":"Crossref","is-referenced-by-count":100,"title":["The Aryl Hydrocarbon Receptor Promotes IL-10 Production by NK Cells"],"prefix":"10.1093","volume":"192","author":[{"given":"Sagie","family":"Wagage","sequence":"first","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beena","family":"John","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan L","family":"Krock","sequence":"additional","affiliation":[{"name":"Abramson Family Cancer Research Institute, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aisling O\u2019Hara","family":"Hall","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise M","family":"Randall","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher L","family":"Karp","sequence":"additional","affiliation":[{"name":"Division of Molecular Immunology, Cincinnati Children\u2019s Hospital Medical Center , Cincinnati, OH 45229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M Celeste","family":"Simon","sequence":"additional","affiliation":[{"name":"Abramson Family Cancer Research Institute, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher A","family":"Hunter","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,2,15]]},"reference":[{"key":"2025032404121756900_r1","doi-asserted-by":"crossref","first-page":"2533","DOI":"10.4049\/jimmunol.153.6.2533","article-title":"Parasite-induced IL-12 stimulates early IFN-\u03b3 synthesis and resistance during acute infection with Toxoplasma gondii","volume":"153","author":"Gazzinelli","year":"1994","journal-title":"J. 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