{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T19:00:10Z","timestamp":1788807610058,"version":"build-2803163510"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"\n Background<\/jats:title>\n IL-17-producing Type 17 T (T17) cells are central drivers of inflammation in both psoriasis and hidradenitis suppurativa (HS), as evidenced by the clinical efficacy of IL-17-targeting therapies. However, therapeutic responses differ substantially between diseases, raising the possibility that the composition and regulation of T17 states are disease context dependent.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To define disease-specific T17 subset composition and regulatory T-cell (Treg) transcriptional programs in psoriasis and HS at single-cell resolution, and to generate hypothesis framework regarding their potential relationship to differential therapeutic responses.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We performed integrated single-cell RNA sequencing (scRNA-seq) analysis of lesional skin from psoriasis (n=20), HS (n=8), atopic dermatitis (AD; n=4), and healthy controls (n=19). T17 subsets were defined based on\n IL17A, IL17F, IFNG<\/jats:italic>\n , and\n IL10<\/jats:italic>\n expression, and\n FOXP3<\/jats:italic>\n expression was used to identify Tregs. Comparative transcriptomic analyses were conducted across diseases to characterize subset composition and functional gene programs.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Psoriasis lesions were enriched in\n IL17A<\/jats:italic>\n +<\/jats:sup>\n IFNG<\/jats:italic>\n +<\/jats:sup>\n T17 cells exhibiting cytotoxic and tissue-resident memory signatures, whereas this subset was markedly reduced in HS (19.83% vs 1.27%). In contrast, HS lesions showed expansion of\n IL17A<\/jats:italic>\n +<\/jats:sup>\n IL17F<\/jats:italic>\n +<\/jats:sup>\n and\n IL17F<\/jats:italic>\n +<\/jats:sup>\n IL10<\/jats:italic>\n -<\/jats:sup>\n T17 subsets, with the\n IL17A<\/jats:italic>\n +<\/jats:sup>\n IL17F<\/jats:italic>\n +<\/jats:sup>\n subset demonstrating enhanced inflammatory (\n TNF, CSF2, IL21, IL1B, CSF3<\/jats:italic>\n ) and proliferative (\n MKI67<\/jats:italic>\n ) programs, along with increased\n IL1R1<\/jats:italic>\n and\n OX40<\/jats:italic>\n expression. Tregs in both diseases showed reduced\n IL10<\/jats:italic>\n and immunoregulatory markers; however, HS Tregs uniquely expressed proinflammatory mediators including\n IL17A, IL17F, CXCL13, IL1B<\/jats:italic>\n , and\n CSF3<\/jats:italic>\n , indicating a more inflammatory transcriptional state. Dual immunohistochemistry identified cells showing nuclear FOXP3 staining together with IL-1\u03b2, IL-17A, or IL-17F protein staining in HS lesions.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n These findings reveal a marked divergence in type 17 immunity between psoriasis and HS. HS is characterized by expansion of\n IL17A<\/jats:italic>\n +<\/jats:sup>\n IL17F<\/jats:italic>\n +<\/jats:sup>\n T17 cells with an IL-1\u2013associated inflammatory program and inflammatory remodeling of Tregs, rather than enrichment of IL-23-responsive\n IL17A<\/jats:italic>\n +<\/jats:sup>\n IFNG<\/jats:italic>\n +<\/jats:sup>\n T17 cells observed in psoriasis. This disease-specific immune architecture provides a hypothesis-generating framework for potentially different responses to pathway-targeted therapies and motivates further evaluation of therapeutic approaches in HS, including dual IL-17A\/IL-17F blockade and IL-1-targeted approaches.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1835460","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T05:32:49Z","timestamp":1786685569000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Type 17 T-cell subset divergence in hidradenitis suppurativa versus psoriasis: a comparative single-cell transcriptomic analysis"],"prefix":"10.3389","volume":"17","author":[{"given":"Nayoung","family":"Park","sequence":"first","affiliation":[{"name":"Department of Biomedical Science and Engineering, Konkuk University","place":["Seoul, Republic of Korea"]},{"name":"Division of Biomedical Engineering, Hankuk University of Foreign Studies","place":["Kyoungki-do, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jongeun","family":"Lee","sequence":"additional","affiliation":[{"name":"Laboratory for Investigative Dermatology, The Rockefeller University","place":["New York, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dayeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Biomedical Engineering, Hankuk University of Foreign Studies","place":["Kyoungki-do, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darshna","family":"Rambhia","sequence":"additional","affiliation":[{"name":"Laboratory for Investigative Dermatology, The Rockefeller University","place":["New York, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaebum","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science and Engineering, Konkuk University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Laboratory of Single-cell Genomics and Population Dynamics, The Rockefeller University","place":["New York, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyue","family":"Cao","sequence":"additional","affiliation":[{"name":"Laboratory of Single-cell Genomics and Population Dynamics, The Rockefeller University","place":["New York, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James G.","family":"Krueger","sequence":"additional","affiliation":[{"name":"Laboratory for Investigative Dermatology, The Rockefeller University","place":["New York, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Younhee","family":"Ko","sequence":"additional","affiliation":[{"name":"Division of Biomedical Engineering, Hankuk University of Foreign Studies","place":["Kyoungki-do, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaehwan","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory for Investigative Dermatology, The Rockefeller University","place":["New York, NY, United States"]},{"name":"Department of Dermatology, University of California, Davis","place":["Sacramento, CA, United States"]},{"name":"Dermatology Section, Veterans Affairs Northern California Health Care System","place":["Mather, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2012.11.005","article-title":"The IL-23\/T17 pathogenic axis in psoriasis is amplified by keratinocyte responses","volume":"34","author":"Lowes","year":"2013","journal-title":"Trends 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