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However, the direct effects of AhR on the development of allergic diseases are not fully understood. The main aim of this study was to elucidate the action of AhR in the development of cutaneous allergies. Initially, the potential for a direct relationship between AhR and the immune cells was investigated in vitro, using murine bone marrow\u2010derived dendritic cells, human epidermal keratinocytes, and the mixed leukocyte reaction assay. Benzo[<jats:italic>a<\/jats:italic>]pyrene (BaP) and 6\u2010formylindolo[3,2\u2010<jats:italic>b<\/jats:italic>]carbazole were used as selective ligands for the AhR. Pretreatment with BaP and\/or 6\u2010formylindolo[3,2\u2010<jats:italic>b<\/jats:italic>]carbazole significantly induced cytokine release by activated keratinocytes and T\u2010cell proliferation, whereas interleukin\u201012 production in bone marrow\u2010derived dendritic cells was reduced by AhR activation. To confirm the in vitro results, in vivo experiments were also performed in T\u2010helper (Th)2\u2010type hapten toluene\u20102,4\u2010diisocyanate\u2010 and Th1\u2010type hapten dinitrochlorobenzene\u2010induced mouse models of allergic dermatitis. Mice were orally administered BaP at 48, 24 and 4\u00a0hours before the final allergen challenge. In the Th2 model, ear\u2010swelling response and scratching behavior were promoted by BaP exposure, which supported the observed significant increases in local cytokine secretion. The infiltration of helper T cells, B cells and dendritic cells into the auricular lymph node was significantly enhanced by BaP administration, although Th1\u2010type immune responses were not influenced by AhR activation. Our findings demonstrate that AhR activation directly activates keratinocytes and T cells, which leads to the exacerbation of Th2\u2010type cutaneous allergy.<\/jats:p>","DOI":"10.1002\/jat.3782","type":"journal-article","created":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T14:11:13Z","timestamp":1549980673000},"page":"936-944","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Direct activation of aryl hydrocarbon receptor by benzo[<i>a<\/i>]pyrene elicits T\u2010helper 2\u2010driven proinflammatory responses in a mouse model of allergic dermatitis"],"prefix":"10.1002","volume":"39","author":[{"given":"Hitoshi","family":"Tajima","sequence":"first","affiliation":[{"name":"Toxicology Division Institute of Environmental Toxicology  4321, Uchimoriya\u2010machi Joso\u2010shi Ibaraki 303\u20100043 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