{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:27:55Z","timestamp":1790659675874,"version":"4.1.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T00:00:00Z","timestamp":1668643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Penn State Dermatology Research Endowment to A.M.N."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,2,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Hidradenitis suppurativa (HS) is a debilitating inflammatory skin disease characterized by painful nodules, drainage and scarring in skin folds. Injectable adalimumab is the only drug approved by the US Food and Drug Administration for the treatment of HS. Although systemic Janus kinase (JAK) inhibitors show promise, serious side-effects have been reported. There are no highly effective topical treatments for HS; furthermore, the contribution of epidermal keratinocytes to the intense inflammation has largely been unexplored.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>We investigated the role of keratinocytes and epidermal immune cells in HS inflammation at all Hurley stages of disease severity. We aimed to determine whether ruxolitinib can mitigate inflammation from keratinocytes and to develop a better understanding of how topical therapeutics might benefit patients with HS.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We used skin samples from 87 patients with HS (Hurley stages I\u2013III) and 39 healthy controls to compare keratinocyte- and immune cell-driven epidermal inflammation, in addition to the response of lesional HS keratinocytes to treatment with interferon (IFN)-\u03b3 and ruxolitinib. We used haematoxylin and eosin staining, immunohistochemistry, immunoblotting and quantitative reverse-transcription polymerase chain reaction assessments in whole skin, isolated epidermis, and cultured keratinocytes from healthy controls and both nonlesional and lesional HS skin to identify and define epidermal and keratinocyte-mediated inflammation in HS and how this may be targeted by therapeutics.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>HS lesional keratinocytes autonomously secreted high levels of chemokines, such as CCL2, CCL3 and CXCL3, which recruited neutrophils, CD8 T cells, and natural killer cells to the epidermis. Keratinocytes were the dominant source of tumour necrosis factor-\u03b1 and interleukin (IL)-6 in HS lesions with little to no contribution from underlying dermal immune cells. In the presence of IFN-\u03b3, which is dependent on immune cell infiltrate in vivo, keratinocytes expressed increased levels of additional cytokines including IL-1\u03b2, IL-12, IL-23 and IL-36\u03b3. The JAK inhibitor ruxolitinib mitigated the expression of inflammatory cytokines and chemokines in HS lesional keratinocytes, thus providing a rationale for future study as a topical treatment for HS.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This study demonstrates that keratinocytes actively recruit immune cells to HS epidermis and interactions between these cells drive a broad inflammatory profile in HS epidermis. Targeting epidermal inflammation in HS with novel topical formulations may be highly efficacious with reduced systemic side-effects.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bjd\/ljac096","type":"journal-article","created":{"date-parts":[[2023,1,21]],"date-time":"2023-01-21T06:10:25Z","timestamp":1674281425000},"page":"407-419","source":"Crossref","is-referenced-by-count":52,"title":["Keratinocytes and immune cells in the epidermis are key drivers of inflammation in hidradenitis suppurativa providing a rationale for novel topical therapies"],"prefix":"10.1093","volume":"188","author":[{"given":"Stephanie L","family":"Schell","sequence":"first","affiliation":[{"name":"Department of Dermatology, The Pennsylvania State University College of Medicine , Hershey, PA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoyuan","family":"Cong","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The Pennsylvania State University College of Medicine , Hershey, PA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mackenzie L","family":"Sennett","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The Pennsylvania State University College of Medicine , Hershey, PA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha L","family":"Gettle","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The Pennsylvania State University College of Medicine , Hershey, PA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy L","family":"Longenecker","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The Pennsylvania State University College of Medicine , Hershey, PA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie R","family":"Goldberg","sequence":"additional","affiliation":[{"name":"General Surgery and Trauma, Mary Washington Medical Center , Fredericksburg, VA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joslyn S","family":"Kirby","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The Pennsylvania State University College of Medicine , Hershey, PA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew F","family":"Helm","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The Pennsylvania State University College of Medicine , Hershey, PA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda M","family":"Nelson","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The Pennsylvania State University College of Medicine , Hershey, PA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,11,17]]},"reference":[{"key":"2023100620082038700_ljac096-B1","first-page":"2","article-title":"Global prevalence of hidradenitis suppurativa and geographical 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placebo-controlled PIONEER trials","volume":"181","author":"Jemec","year":"2019","journal-title":"Br J Dermatol"},{"key":"2023100620082038700_ljac096-B5","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.jaad.2019.02.068","article-title":"North American clinical management guidelines for hidradenitis suppurativa: a publication from the United States and Canadian Hidradenitis Suppurativa Foundations: part II: topical, intralesional, and systemic medical management","volume":"81","author":"Alikhan","year":"2019","journal-title":"J Am Acad Dermatol"},{"key":"2023100620082038700_ljac096-B6","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1016\/j.jaad.2020.05.007","article-title":"The effect of subcutaneous brodalumab on clinical disease activity in hidradenitis suppurativa: an open-label cohort study","volume":"83","author":"Frew","year":"2020","journal-title":"J Am Acad 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hidradenitis suppurativa","volume":"173","author":"Kelly","year":"2015","journal-title":"Br J Dermatol"},{"key":"2023100620082038700_ljac096-B11","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1111\/j.1365-2133.2011.10254.x","article-title":"Elevated levels of tumour necrosis factor (TNF)-\u03b1, interleukin (IL)-1\u03b2 and IL-10 in hidradenitis suppurativa skin: a rationale for targeting TNF-\u03b1 and IL-1\u03b2","volume":"164","author":"van der Zee","year":"2011","journal-title":"Br J Dermatol"},{"key":"2023100620082038700_ljac096-B12","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1111\/j.1365-2133.2011.10698.x","article-title":"Adalimumab (antitumour necrosis factor-\u03b1) treatment of hidradenitis suppurativa ameliorates skin inflammation: an in situ and ex vivo study","volume":"166","author":"van der Zee","year":"2012","journal-title":"Br J 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