{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T04:11:49Z","timestamp":1792383109160,"version":"4.4.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T00:00:00Z","timestamp":1731369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007775","name":"UCB","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007775","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Isabel Katz BA"},{"name":"UCB in accordance with Good Publication Practice"},{"DOI":"10.13039\/501100008213","name":"GPP","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008213","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hidradenitis suppurativa (HS) is a chronic relapsing inflammatory skin disease associated with significant comorbidities and poor quality of life. Despite uncertainty about pathways driving inflammation in HS lesions, the cytokines interleukin (IL)-17A and IL-17F have been shown to be upregulated in patients with HS. Previous studies have demonstrated that the monoclonal IgG1 antibody bimekizumab selectively inhibits IL-17F in addition to IL-17A.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To further investigate the roles of IL-17A and IL-17F in HS pathogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>RNA sequencing (RNAseq) was conducted on skin biopsies taken at baseline and after treatment at week 12 of a phase II proof-of-concept study of bimekizumab in patients with moderate-to-severe HS. Differentially expressed genes were identified between baseline lesional and nonlesional samples and between lesional samples before and after bimekizumab treatment, to describe molecular disease mechanisms and treatment effect. Human hair follicular keratinocytes (HHFK) were cultured and treated with a supernatant of stimulated T helper (Th)17 cells in combination with anti-IL-17A, anti-IL-17F, anti-IL-17A and anti-IL-17F, or IgG control antibodies. Total mRNA was analysed by RNAseq. Cellular supernatants from the stimulated HHFKs were used as a source of Th17-induced chemoattractants in neutrophil chemotaxis assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>RNAseq revealed that the most prominently upregulated genes in HS lesions included those associated with neutrophil biology. Bimekizumab treatment resulted in reduced expression of these genes. The extent of reduction in gene expression was dependent on achieving HiSCR50 (\u2265 50% reduction from baseline in the total abscess and inflammatory nodule count, with no increase from baseline in abscess or draining tunnel count). In vitro dual inhibition of IL-17A and IL-17F had greater attenuation of Th17-induced HS-associated genes and neutrophil migration in HHFKs vs. IL-17A or IL-17F inhibition alone. In situ hybridization found that IL-17A- and IL-17F-producing cells in HS lesions can lack the IL-23 receptor and IL-1\u03b2 could induce IL-23-independent IL-17F expression in vitro. Furthermore, mucosal-associated invariant cells in HS tunnels expressed IL-17F and IL-1 receptor type 1. IL-1\u03b2-, IL-17A- and IL-17F-expressing cells were found to be co-localized in HS lesions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These data support the hypothesis that IL-17A and IL-17F play central roles in HS, a neutrophilic dermatosis. The presence of IL-1\u03b2 may partly explain the high expression of IL-17F in lesional HS tissue.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bjd\/ljae442","type":"journal-article","created":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T15:26:13Z","timestamp":1731079573000},"page":"660-671","source":"Crossref","is-referenced-by-count":28,"title":["The roles of interleukin (IL)-17A and IL-17F in hidradenitis suppurativa pathogenesis: evidence from human\n                    <i>in vitro<\/i>\n                    preclinical experiments and clinical samples"],"prefix":"10.1093","volume":"192","author":[{"given":"Joseph","family":"Rastrick","sequence":"first","affiliation":[{"name":"UCB , Slough ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Edwards","sequence":"additional","affiliation":[{"name":"UCB , Slough ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex 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