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However, whether soluble adenylate cyclase (sAC) (encoded by the <jats:italic>ADCY10<\/jats:italic> gene), which is an important source for cAMP, is involved in Th17 cell\u2010mediated inflammation or could be an alternative therapeutic target in psoriasis is unknown. We have utilized the imiquimod model of murine psoriasiform dermatitis to address this question. <jats:italic>Adcy10<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice had reduced erythema, scaling and swelling in the skin and reduced CD4+ IL17+ cell numbers in the draining lymph nodes, compared with wild\u2010type mice after induction of psoriasiform dermatitis with imiquimod. Keratinocyte\u2010specific knock out of <jats:italic>Adcy10<\/jats:italic> had no effect on imiquimod\u2010induced ear swelling suggesting keratinocyte sAC has no role in imiquimod\u2010induced inflammation. During Th17 polarization in vitro, naive T cells from <jats:italic>Adcy10<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice exhibited reduced IL17 secretion and IL\u201017+ T\u2010cell proliferation suggesting that differentiation into Th17 cells is suppressed without sAC activity. Interestingly, loss of sAC did not impact the expression of Th17 lineage\u2010defining transcription factors (such as <jats:italic>Rorc<\/jats:italic> and <jats:italic>cMaf<\/jats:italic>) but rather was required for CREB\u2010dependent gene expression, which is known to support Th17 cell gene expression. Finally, topical application of small molecule sAC inhibitors (sACi) reduced imiquimod\u2010induced psoriasiform dermatitis and <jats:italic>Il17<\/jats:italic> gene expression in the skin. Collectively, these findings demonstrate that sAC is important for psoriasiform dermatitis in mouse skin. sACi may provide an alternative class of topical therapeutics for Th17\u2010mediated skin diseases.<\/jats:p>","DOI":"10.1111\/exd.14811","type":"journal-article","created":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T12:44:50Z","timestamp":1681217090000},"page":"1051-1062","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Soluble adenylyl cyclase contributes to imiquimod\u2010mediated inflammation and is a potential therapeutic target in psoriasis"],"prefix":"10.1111","volume":"32","author":[{"given":"Jaewon","family":"You","sequence":"first","affiliation":[{"name":"Department of Dermatology Weill Cornell Medicine  New York City New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Reilly","sequence":"additional","affiliation":[{"name":"Department of 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