{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T02:50:32Z","timestamp":1793155832159,"version":"4.5.0"},"reference-count":69,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T00:00:00Z","timestamp":1694476800000},"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":"<jats:p>Durable psoriasis improvement has been reported in a subset of psoriasis patients after treatment withdrawal of biologics blocking IL-23\/Type 17 T-cell (T17) autoimmune axis. However, it is not well understood if systemic blockade of the IL-23\/T17 axis promotes immune tolerance in psoriasis skin. The purpose of the study was to find translational evidence that systemic IL-17A blockade promotes regulatory transcriptome modification in human psoriasis skin immune cell subsets. We analyzed human psoriasis lesional skin 6\u00a0mm punch biopsy tissues before and after systemic IL-17A blockade using the muti-genomics approach integrating immune cell-enriched scRNA-seq (n = 18), microarray (n = 61), and immunohistochemistry (n = 61) with repository normal control skin immune cell-enriched scRNA-seq (n = 10) and microarray (n = 8) data. For the T17 axis transcriptome, systemic IL-17A blockade depleted 100% of <jats:italic>IL17A<\/jats:italic><jats:sup>+<\/jats:sup> T-cells and 95% of <jats:italic>IL17F<\/jats:italic><jats:sup>+<\/jats:sup> T-cells in psoriasis skin. The expression of <jats:italic>IL23A<\/jats:italic> in DC subsets was also downregulated by IL-17A blockade. The expression of IL-17-driven inflammatory mediators (<jats:italic>IL36G<\/jats:italic>, <jats:italic>S100A8<\/jats:italic>, <jats:italic>DEFB4A<\/jats:italic>, and <jats:italic>DEFB4B<\/jats:italic>) in suprabasal keratinocytes was correlated with psoriasis severity and was downregulated by IL-17A blockade. For the regulatory DC transcriptome, the proportion of regulatory semimature DCs expressing regulatory DC markers of <jats:italic>BDCA-3<\/jats:italic> (<jats:italic>THBD<\/jats:italic>) and <jats:italic>DCIR<\/jats:italic> (<jats:italic>CLEC4A<\/jats:italic>) was increased in posttreatment psoriasis lesional skin compared to pretreatment psoriasis lesional skin. In addition, IL-17A blockade induced higher expression of <jats:italic>CD1C<\/jats:italic> and <jats:italic>CD14<\/jats:italic>, which are markers of CD1c<jats:sup>+<\/jats:sup> CD14<jats:sup>+<\/jats:sup> dendritic cell (DC) subset that suppresses antigen-specific T-cell responses, in posttreatment regulatory semimature DCs compared to pretreatment regulatory semimature DCs. In conclusion, systemic IL-17A inhibition not only blocks the entire IL-23\/T17 cell axis but also promotes regulatory gene expression in regulatory DCs in human psoriasis skin.<\/jats:p>","DOI":"10.3389\/fimmu.2023.1250504","type":"journal-article","created":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T04:41:10Z","timestamp":1694580070000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":30,"title":["Multi-omics segregate different transcriptomic impacts of anti-IL-17A blockade on type 17 T-cells and regulatory immune cells in psoriasis skin"],"prefix":"10.3389","volume":"14","author":[{"given":"Jaehwan","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jongmi","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norma","family":"Kunjravia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darshna","family":"Rambhia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inna","family":"Cueto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasuma","family":"Chaparala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Younhee","family":"Ko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Garcet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyue","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James G.","family":"Krueger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,9,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2013.11.013","article-title":"Psoriasis prevalence among adults in the United States","volume":"70","author":"Rachakonda","year":"2014","journal-title":"J Am Acad Dermatol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2021.2007","article-title":"Psoriasis prevalence in adults in the United States","volume":"157","author":"Armstrong","year":"2021","journal-title":"JAMA Dermatol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-042915-103905","article-title":"Highly effective new treatments for psoriasis target the IL-23\/type 17 T cell autoimmune axis","volume":"68","author":"Kim","year":"2017","journal-title":"Annu Rev Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2007.08068.x","article-title":"Obesity in psoriasis: the metabolic, clinical and therapeutic implications. 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