{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T18:22:27Z","timestamp":1783102947938,"version":"3.54.6"},"reference-count":52,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"27","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273939"],"award-info":[{"award-number":["82273939"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81874361"],"award-info":[{"award-number":["81874361"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Double First Class University Project","award":["CPU2022QZ31"],"award-info":[{"award-number":["CPU2022QZ31"]}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,7,3]]},"abstract":"<jats:p>\n                    Despite the well-established role of interleukin-17 (IL-17)\u2013producing \u03b3\u03b4 T cells (\u03b3\u03b4T17 cells) in autoimmune inflammations, key factors to trigger the activation of \u03b3\u03b4T17 cells remain largely unknown. Here, we show that aryl hydrocarbon receptor (AhR) is markedly reduced upon \u03b3\u03b4T17 cell activation. AhR deficiency and pharmacological activation promotes and suppresses \u03b3\u03b4T17 cell activation, respectively. Mechanistically, AhR deficiency strengthens heat shock protein family A member 9 (HSPA9)-mediated competition with F-box and WD-40 domain protein 11(FBXW11) for binding to RBP-j-associated molecule (RAM) domain of Notch intracellular domain (NICD), which impairs FBXW11-dependent NICD ubiquitination to increase NICD occupancy at the\n                    <jats:italic toggle=\"yes\">Rorc<\/jats:italic>\n                    enhancer to drive \u03b3\u03b4T17 cell activation. Consistently, AhR deficiency increases the proportion of \u03b3\u03b4T17 cells and the disease severity in psoriasis-like dermatitis mice and colitis mice, which is almost entirely reversed by pretreatment with either adeno-associated virus (AAV)-sh\n                    <jats:italic toggle=\"yes\">Hspa9<\/jats:italic>\n                    or AAV-sh\n                    <jats:italic toggle=\"yes\">Notch1<\/jats:italic>\n                    . Collectively, these findings identify AhR deficiency as a key driver of aberrant \u03b3\u03b4T17 activation, uncover a \u03b3\u03b4T17 activation mechanism via HSPA9\/FBXW11-mediated suppression of NICD ubiquitination, and provide a strong mechanistic basis for AhR agonists as therapeutics in autoimmune inflammations.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aef7793","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T17:58:28Z","timestamp":1783101508000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Aryl hydrocarbon receptor deficiency triggers the activation of \u03b3\u03b4T17 cells to exacerbate autoimmune inflammation"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-8765-0645","authenticated-orcid":true,"given":"Yue","family":"He","sequence":"first","affiliation":[{"name":"Department of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Long Mian Avenue, Nanjing 211198, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9283-0543","authenticated-orcid":true,"given":"Yilei","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Long Mian Avenue, Nanjing 211198, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Long Mian Avenue, Nanjing 211198, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuanming","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Long Mian Avenue, Nanjing 211198, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8783-5579","authenticated-orcid":true,"given":"Yanrong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Long Mian Avenue, Nanjing 211198, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Long Mian Avenue, Nanjing 211198, 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