{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:23:48Z","timestamp":1787163828937,"version":"build-2736575974"},"reference-count":96,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Dermatology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Atopic dermatitis (AD) is a chronic inflammatory dermatitis underpinned by Type 2 inflammation driven by cytokines such as IL\u20104 and IL\u201013. It is characterized by skin barrier dysfunction, Th2 immune deviation, and pruritus. While biologics and oral Janus kinase (JAK) inhibitors demonstrate high therapeutic efficacy by targeting cytokines that exert their effects via the JAK, specifically IL\u20104, IL\u201013, and IL\u201031, comprehensive disease control requires additional approaches that modulate JAK\u2010independent pathways. Factors such as TNF\u2010\u03b1, IL\u201025, IL\u201033, microbial antigens, and physical stimuli activate mitogen\u2010activated protein kinase and nuclear factor\u2010\u03baB signaling in a JAK\u2010independent manner, sustaining the disease activity. Consequently, in some cases, a strategy incorporating topical treatment that inhibits JAK\u2010independent pathways is indispensable alongside systemic treatment. One potential strategy of this kind involves the aryl hydrocarbon receptor (AhR), ligand\u2010activated transcription factor. Under Th2\u2010polarized conditions, the expression of indoleamine 2,3\u2010dioxygenase 1 (IDO1) is downregulated, limiting the availability of tryptophan\u2010derived metabolites. This scarcity of endogenous AhR ligands subsequently compromises physiological AhR signaling. Tapinarof, a therapeutic AhR\u2010modulating agent (TAMA), activates AhR without generating excessive reactive oxygen species. This exerts multiple effects: enhancing antioxidant defenses via nuclear factor erythroid 2\u2010related factor 2 (NRF2) activation, restoring barrier dysfunction, suppressing Th2 inflammation, and correcting abnormalities associated with pruritus\u2010related molecules. Furthermore, clinical trials of tapinarof have demonstrated improvement of the disease activity and pruritus, with efficacy intensifying over long\u2010term treatment. Although adverse events such as folliculitis, acne, contact dermatitis, and headache occur, they are generally manageable by adjusting the frequency of application based on their reversibility and time of onset. Moreover, considering potential antagonism by IL\u201024 induced by tapinarof, combining tapinarof with systemic agents, topical therapies, or phototherapy may serve to optimize the therapeutic effects. In conclusion, AhR functions as a molecular hub integrating AD pathology, and the TAMA tapinarof expands therapeutic strategies in the treatment of AD.<\/jats:p>","DOI":"10.1111\/1346-8138.70295","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T05:26:08Z","timestamp":1777526768000},"page":"867-879","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Tapinarof as a Therapeutic Aryl Hydrocarbon Receptor\u2010Modulating Agent in the Treatment of Atopic Dermatitis"],"prefix":"10.1111","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1472-1864","authenticated-orcid":false,"given":"Gaku","family":"Tsuji","sequence":"first","affiliation":[{"name":"Department of Dermatology Graduate School of Medical Sciences, Kyushu University  Fukuoka Japan"},{"name":"Research and Clinical Center for Yusho and Dioxin, Kyushu University Hospital  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6209-7923","authenticated-orcid":false,"given":"Yoko","family":"Fuyuno","sequence":"additional","affiliation":[{"name":"Department of Dermatology Graduate School of Medical Sciences, Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8719-8686","authenticated-orcid":false,"given":"Koji","family":"Kawamura","sequence":"additional","affiliation":[{"name":"Department of Dermatology Graduate School of Medical Sciences, Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2198-8965","authenticated-orcid":false,"given":"Ayako","family":"Yumine","sequence":"additional","affiliation":[{"name":"Department of Dermatology Graduate School of Medical Sciences, Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2503-8449","authenticated-orcid":false,"given":"Masaki","family":"Takemura","sequence":"additional","affiliation":[{"name":"Department of Dermatology Graduate School of Medical Sciences, Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6389-9285","authenticated-orcid":false,"given":"Yasutaka","family":"Mitamura","sequence":"additional","affiliation":[{"name":"Department of Dermatology Graduate School of Medical Sciences, Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9216-945X","authenticated-orcid":false,"given":"Kazuhiko","family":"Yamamura","sequence":"additional","affiliation":[{"name":"Department of Dermatology Graduate School of Medical Sciences, Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2811-8273","authenticated-orcid":false,"given":"Takeshi","family":"Nakahara","sequence":"additional","affiliation":[{"name":"Department of Dermatology Graduate School of Medical Sciences, Kyushu University  Fukuoka Japan"},{"name":"Research and Clinical Center for Yusho and Dioxin, Kyushu University Hospital  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alit.2016.12.002"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/1346\u20108138.15664"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2024.04.009"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/life11090927"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2011.24"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2010.277"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2019.08.006"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm4061217"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.4168\/aair.2019.11.5.593"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201038209\u2010x"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(21)00588\u20102"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(20)30732\u20107"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2020.1406"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13555\u2010022\u201000738\u20106"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2019.12.015"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2021.10.027"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/1346\u20108138.17451"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00403\u2010014\u20101481\u20107"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0304\u20104165(02)00485\u20103"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010025\u201002500\u20108"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281\u2010013\u20100394\u20104"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2023.168296"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22020708"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2010.10.017"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2011.194"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2011.359"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010019\u201047138\u2010z"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph17080980"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12010172"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01004"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.15.5492\u20105505.2002"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2022.08.048"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1421346"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.2174\/138920011795016818"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101530"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cotox.2017.11.002"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/792639"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2008.122"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2024.109958"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.475624"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2024.11.003"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22031104"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2022.101573"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2024.2430420"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2013.92"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0701764104"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2013.04.031"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2020.10.085"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/1346\u20108138.12717"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI65642"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2023.12.013"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2017.05.004"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2023.10.002"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox13060732"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2025.117559"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.3389\/falgy.2024.1323405"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2018.11.036"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.09.055"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V83.5.1408.1408"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2024.109923"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1159\/000128584"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1111\/pai.70265"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2016.06.627"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2021.05.011"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.3443"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2015.07.011"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2015.6"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2017.322"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2023.07.027"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2009.04.001"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2023.03.1662"},{"key":"e_1_2_11_73_1","doi-asserted-by":"publisher","DOI":"10.3389\/jcia.2024.13418"},{"key":"e_1_2_11_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2011.12.008"},{"key":"e_1_2_11_75_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpbreports.7.4_123"},{"key":"e_1_2_11_76_1","doi-asserted-by":"publisher","DOI":"10.1111\/exd.14541"},{"key":"e_1_2_11_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.109705"},{"key":"e_1_2_11_78_1","doi-asserted-by":"publisher","DOI":"10.4049\/immunohorizons.2100055"},{"key":"e_1_2_11_79_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.14769"},{"key":"e_1_2_11_80_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241914633"},{"key":"e_1_2_11_81_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.745997"},{"key":"e_1_2_11_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alit.2022.04.003"},{"key":"e_1_2_11_83_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-44866-0"},{"key":"e_1_2_11_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2009.03.007"},{"key":"e_1_2_11_85_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3614"},{"key":"e_1_2_11_86_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9030891"},{"key":"e_1_2_11_87_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2020.05.135"},{"key":"e_1_2_11_88_1","doi-asserted-by":"publisher","DOI":"10.1111\/1346\u20108138.17423"},{"key":"e_1_2_11_89_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfx179"},{"key":"e_1_2_11_90_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2016.01.010"},{"key":"e_1_2_11_91_1","doi-asserted-by":"publisher","DOI":"10.1159\/000382031"},{"key":"e_1_2_11_92_1","doi-asserted-by":"publisher","DOI":"10.1080\/09546634.2025.2517388"},{"key":"e_1_2_11_93_1","doi-asserted-by":"publisher","DOI":"10.1111\/cod.14535"},{"key":"e_1_2_11_94_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2024.110322"},{"key":"e_1_2_11_95_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.13437"},{"key":"e_1_2_11_96_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21249412"},{"key":"e_1_2_11_97_1","doi-asserted-by":"publisher","DOI":"10.1111\/1346\u20108138.70158"}],"container-title":["The Journal of Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1346-8138.70295","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/1346-8138.70295","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1346-8138.70295","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T05:31:40Z","timestamp":1780464700000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1346-8138.70295"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,29]]},"references-count":96,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1111\/1346-8138.70295"],"URL":"https:\/\/doi.org\/10.1111\/1346-8138.70295","archive":["Portico"],"relation":{},"ISSN":["0385-2407","1346-8138"],"issn-type":[{"value":"0385-2407","type":"print"},{"value":"1346-8138","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,29]]},"assertion":[{"value":"2026-02-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}