{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:06:30Z","timestamp":1790856390400,"version":"4.1.0"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T00:00:00Z","timestamp":1624492800000},"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:sec><jats:title>Objectives<\/jats:title><jats:p>Psoriatic arthritis (PsA) is a chronic inflammatory disease associated with psoriasis. Janus Kinase inhibitors (JAKi) have emerged as an encouraging class of drugs for the treatment of PsA. Here, we compare the effect of four JAKi on primary PsA synovial fibroblasts (PsAFLS) activation, metabolic function, and invasive and migratory capacity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Primary PsAFLS were isolated and cultured with JAKi (Peficitinib, Filgotinib, Baricitinib and Upadacitinib) in the presence of Oncostatin M (OSM). pSTAT3 expression in response to OSM was quantified by Western Blot analysis. Pro-inflammatory cytokines\/chemokines were quantified by ELISA and cell migration by wound-repair scratch assays. Invasive capacity was examined using Matrigel\u2122 invasion chambers and MMP multiplex MSD assays. PsAFLS bioenergetics was assessed using the Seahorse XF<jats:sup>e<\/jats:sup>\u00a0Extracellular Flux Analyzer, which simultaneously quantifies two energetic pathways- glycolysis (ECAR) and oxidative phosphorylation (OCR). In parallel, inflammatory, invasive, and migratory genes were quantified by RT-PCR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>OSM induces pSTAT3 expression in PsAFLS. OSM-induced secretion of MCP-1 and IL-6 was inhibited by all JAKi with Peficitinib, Baricitinib and Upadacitinib showing the greatest effect. In contrast, JAKi had no significant impact on IL-8 expression in response to OSM. PsAFLS cell invasion, migratory capacity and MMP1, 3, and 9 were suppressed following JAKi treatment, with Peficitinib showing the greatest effect. These functional effects were accompanied by a change in the cellular bioenergetic profile of PsAFLS, where JAKi significantly decreased glycolysis and the ECAR\/OCR, resulting in a shift to a more quiescent phenotype, with Peficitinib demonstrating the most pronounced effect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study demonstrates that JAK\/STAT signalling mediates the complex interplay between inflammation and cellular metabolism in PsA pathogenesis. This inhibition shows effective suppression of inflammatory mechanisms that drive pathogenic functions of PsAFLS, further supporting the role of JAKi as a therapeutic target for the treatment of PsA.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2021.672461","type":"journal-article","created":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T06:41:03Z","timestamp":1624516863000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["Targeting JAK-STAT Signalling Alters PsA Synovial Fibroblast Pro-Inflammatory and Metabolic Function"],"prefix":"10.3389","volume":"12","author":[{"given":"Aisling","family":"O\u2019Brien","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan Mary","family":"Hanlon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viviana","family":"Marzaioli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siobhan C.","family":"Wade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keelin","family":"Flynn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ursula","family":"Fearon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas J.","family":"Veale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,6,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30830-4","article-title":"The Pathogenesis of Psoriatic Arthritis","volume":"391","author":"Veale","year":"2018","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-018-4012-7","article-title":"Psoriatic Arthritis: Tissue-Directed Inflammation","volume":"37","author":"Cafaro","year":"2018","journal-title":"Clin Rheumatol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1007\/s11926-011-0181-y","article-title":"Synovitis in Psoriatic Arthritis: Immunohistochemistry, Comparisons With Rheumatoid Arthritis, and Effects of Therapy","volume":"13","author":"van Kuijk","year":"2011","journal-title":"Curr Rheumatol Rep"},{"key":"B4","article-title":"Patterns of Cytokine Production in Psoriatic Synovium","volume":"25","author":"Ritchlin","year":"1998","journal-title":"J Rheumatol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1186\/s13075-019-2088-3","article-title":"Enhanced Angiogenic Function in Response to Fibroblasts From Psoriatic Arthritis Synovium Compared to Rheumatoid Arthritis","volume":"21","author":"Fromm","year":"2019","journal-title":"Arthritis Res Ther"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1053\/sarh.2002.50004","article-title":"Diagnostic Usefulness of Synovial Vascular Morphology in Chronic Arthritis. 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