{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T18:54:13Z","timestamp":1774896853129,"version":"3.50.1"},"reference-count":43,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T00:00:00Z","timestamp":1647820800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Interleukin (IL)\u201012 and IL\u201023 are pro\u2010inflammatory cytokines produced by dendritic cells (DCs) and associated with Psoriasis (Pso) and Psoriatic Arthritis (PsA) pathogenesis. Tofacitinib, a Janus kinase inhibitor, effectively suppresses inflammatory cascades downstream the IL\u201012\/IL\u201023 axis in Pso and PsA patients. Here, we investigated whether Tofacitinib directly regulates IL\u201012\/IL\u201023 production in DCs, and how this regulation reflects responses to Tofacitinib in Pso patients. We treated monocyte\u2010derived dendritic cells and myeloid dendritic cells with Tofacitinib and stimulated cells with either lipopolysaccharide (LPS) or a combination of LPS and IFN\u2010\u03b3. We assessed gene expression by qPCR, obtained skin microarray and blood Olink data and clinical parameters of Pso patients treated with Tofacitinib from public data sets. Our results indicate that in DCs co\u2010stimulated with LPS and IFN\u2010\u03b3, but not with LPS alone, Tofacitinib leads to the decreased expression of IL\u201023\/IL\u201012\u00a0shared subunit <jats:italic>IL12B<\/jats:italic> (p40). In Tofacitinib\u2010treated Pso patients, IL\u201012 expression and psoriasis area and severity index (PASI) are significantly reduced in patients with higher IFN\u2010\u03b3 at baseline. These findings demonstrate for the first time that Tofacitinib suppresses IL\u201023\/IL\u201012\u00a0shared subunit <jats:italic>IL12B<\/jats:italic> in DCs upon active IFN\u2010\u03b3 signaling, and that Pso patients with higher IFN\u2010\u03b3 baseline levels display improved clinical response after Tofacitinib treatment.<\/jats:p>","DOI":"10.1111\/exd.14566","type":"journal-article","created":{"date-parts":[[2022,3,17]],"date-time":"2022-03-17T10:00:13Z","timestamp":1647511213000},"page":"962-969","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Suppression of IL\u201012\/IL\u201023 p40 subunit in the skin and blood of psoriasis patients by Tofacitinib is dependent on active interferon\u2010\u03b3 signaling in dendritic cells: Implications for the treatment of psoriasis and interferon\u2010driven diseases"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2892-4814","authenticated-orcid":false,"given":"Nanette L. A.","family":"Vincken","sequence":"first","affiliation":[{"name":"Center for Translational Immunology Department of Immunology University Medical Center Utrecht Utrecht University  Utrecht The Netherlands"},{"name":"Department of Rheumatology and Clinical Immunology University Medical Center Utrecht Utrecht University  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paco M. J.","family":"Welsing","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology University Medical Center Utrecht Utrecht University  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra C.","family":"Silva\u2010Cardoso","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology Department of Immunology University Medical Center Utrecht Utrecht University  Utrecht The Netherlands"},{"name":"Department of Rheumatology and Clinical Immunology University Medical Center Utrecht Utrecht University  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cornelis\u00a0P.\u00a0J.","family":"Bekker","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology Department of Immunology University Medical Center Utrecht Utrecht University  Utrecht The Netherlands"},{"name":"Department of Rheumatology and Clinical Immunology University Medical Center Utrecht Utrecht University  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana P.","family":"Lopes","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology Department of Immunology University Medical Center Utrecht Utrecht University  Utrecht The Netherlands"},{"name":"Department of Rheumatology and Clinical Immunology University Medical Center Utrecht Utrecht University  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel","family":"Olde Nordkamp","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology Department of Immunology University Medical Center Utrecht Utrecht University  Utrecht The Netherlands"},{"name":"Department of Rheumatology and Clinical Immunology University Medical Center Utrecht Utrecht University  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmerik\u00a0F.\u00a0A.","family":"Leijten","sequence":"additional","affiliation":[{"name":"Center for Translational Immunology Department of Immunology University Medical Center Utrecht Utrecht University  Utrecht The Netherlands"},{"name":"Department of Rheumatology and Clinical Immunology University Medical Center Utrecht Utrecht University  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy R. 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