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The activity of PDE4 has been attributed to various inflammatory conditions, leading to the development and approval of PDE4 inhibitors as host\u2010directed therapeutics in humans. For example, the topical PDE4 inhibitor, crisaborole, is approved for the treatment of mild\u2010to\u2010moderate atopic dermatitis and has shown efficacy in patients with psoriasis. However, the role of crisaborole in regulating the immunopathogenesis of inflammatory skin diseases and infection is not entirely known. Therefore, we evaluated the effects of crisaborole in multiple mouse models, including psoriasis\u2010like dermatitis, AD\u2010like skin inflammation with and without filaggrin mutations, and <jats:italic>Staphylococcus aureus<\/jats:italic> skin infection. We discovered that crisaborole dampens myeloid cells and itch in the skin during psoriasis\u2010like dermatitis. Furthermore, crisaborole was effective in reducing skin inflammation in the context of filaggrin deficiency. Importantly, crisaborole reduced <jats:italic>S. aureus<\/jats:italic> skin colonization during AD\u2010like skin inflammation. However, crisaborole was not efficacious in treating <jats:italic>S. aureus<\/jats:italic> skin infections, even as adjunctive therapy to antibiotics. Taken together, we found that crisaborole reduced itch during psoriasis\u2010like dermatitis and decreased <jats:italic>S. aureus<\/jats:italic> skin colonization upon AD\u2010like skin inflammation, which act as additional mechanisms by which crisaborole dampens the immunopathogenesis in mouse models of inflammatory skin diseases. Further examination is warranted to translate these preclinical findings to human disease.<\/jats:p>","DOI":"10.1111\/exd.14722","type":"journal-article","created":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T04:14:21Z","timestamp":1670040861000},"page":"425-435","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Crisaborole efficacy in murine models of skin inflammation and <scp><i>Staphylococcus aureus<\/i><\/scp> infection"],"prefix":"10.1111","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0022-2848","authenticated-orcid":false,"given":"Christine","family":"Youn","sequence":"first","affiliation":[{"name":"Department of Dermatology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dustin A.","family":"Dikeman","sequence":"additional","affiliation":[{"name":"Department of Dermatology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyn","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Dermatology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Dermatology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8213-3621","authenticated-orcid":false,"given":"Sabrina J.","family":"Nolan","sequence":"additional","affiliation":[{"name":"Department of Dermatology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3447-1284","authenticated-orcid":false,"given":"Martin P.","family":"Alphonse","sequence":"additional","affiliation":[{"name":"Department of Dermatology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel P.","family":"Joyce","sequence":"additional","affiliation":[{"name":"Department of Dermatology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Dermatology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Meixiong","sequence":"additional","affiliation":[{"name":"The Solomon H. 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