{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:55:21Z","timestamp":1790751321172,"version":"4.1.0"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"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 Introduction<\/jats:title>\n \n IL-23\u2013targeted therapies have demonstrated clinical efficacy in psoriatic arthritis (PsA), primarily through the reduction of IL-17A\u2013driven inflammation. Consequently, most studies have focused on classical, high IL-17A-producing, CCR6\n +<\/jats:sup>\n CXCR3\n -<\/jats:sup>\n CCR4\n +<\/jats:sup>\n Th17 cells. In contrast, the impact of IL\u201123 signaling on CCR6\n +<\/jats:sup>\n CXCR3\n +<\/jats:sup>\n CCR4\n -<\/jats:sup>\n Th17.1 cells \u2014traditionally characterized by high IFN-\u03b3 and low IL-17A production\u2014remains largely unexplored, despite their recognized pathogenicity in autoimmune disease. The aim of this study was to characterize the effects of IL-23 on human memory Th17.1 cells.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Peripheral blood mononuclear cells (PBMCs) from treatment-naive patients with early PsA were stimulated in the presence of IL-23 or anti-IL-23 antibody before quantifying IL-17A and IFN-\u03b3 secretion. Additionally, human memory CCR6\n -<\/jats:sup>\n Th1, CCR6\n +<\/jats:sup>\n Th17.1 and CCR6+ Th17 cells from healthy donors were sorted and analyzed ex vivo for\n IL23R<\/jats:italic>\n ,\n TBX21<\/jats:italic>\n and\n RORC<\/jats:italic>\n expression using RT-qPCR. Sorted Th17.1, Th17 and Th1 cells were subsequently cultured alone or cocultured with IL-23-producing monocytes. Cultures received either exogenous IL-23 or IL-23 inhibition before analyzing IL-17A and IFN-\u03b3 secretion.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n As expected, IL-23 stimulation induced IL-17A in PsA PBMCs, whereas IL-23 inhibition reduced IL-17A secretion but did not affect IFN-\u03b3. In healthy donor PBMCs, ex vivo IL-23R expression was restricted to memory CCR6\n +<\/jats:sup>\n Th17 and Th17.1 cells. Remarkably, IL-23 stimulation of Th17.1 cells significantly increased IFN-\u03b3 without affecting IL-17A secretion. Compared to monoculture, cocultures with monocytes increased IFN-\u03b3 secretion in Th17.1 and classical Th1 cells, and IL-17A secretion in Th17 and Th17.1 cells. Additional IL-23 stimulated IL-17A in both Th17 and Th17.1 cocultures, while unexpectedly reducing IFN-\u03b3 in Th17.1 cells. In contrast, IL-23 inhibition reduced IL-17A secretion in Th17 and Th17.1 cells without affecting IFN-\u03b3 production.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n IL-23 exerts distinct effects on Th17.1 compared to Th17 cells. We show a role for IL-23 in IFN-\u03b3 upregulation in Th17.1 cells, which is reversed in the presence of monocytes. In co-culture with monocytes, Th17.1 cells progress to a pathogenic IL-17A\n high<\/jats:sup>\n IFN-\u03b3\n high<\/jats:sup>\n profile, which is further elevated by IL-23 stimulation and reduced upon IL-23 neutralization. We show that IL-23 drives Th17.1 plasticity and underscore the therapeutic relevance of neutralizing IL-23 in the suppression of these pathogenic IL-17A\n high<\/jats:sup>\n IFN-\u03b3\n high<\/jats:sup>\n Th17.1 cells.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1793184","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:00:06Z","timestamp":1790748006000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["IL-23 and monocyte interactions redirect human Th17.1 cells to an IL-17AhighIFN-\u03b3high potentially pathogenic profile"],"prefix":"10.3389","volume":"17","author":[{"given":"Bennie","family":"van Heeswijk","sequence":"first","affiliation":[{"name":"Department of Rheumatology, Erasmus MC, University Medical Center","place":["Rotterdam, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wida","family":"Razawy","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Erasmus MC, University Medical Center","place":["Rotterdam, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Davelaar","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Erasmus MC, University Medical Center","place":["Rotterdam, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Marie M.C.","family":"Mus","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Erasmus MC, University Medical Center","place":["Rotterdam, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick S.","family":"Asmawidjaja","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Erasmus MC, University Medical Center","place":["Rotterdam, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter J.M.","family":"Leenen","sequence":"additional","affiliation":[{"name":"Department of Immunology, Erasmus MC, University Medical Center","place":["Rotterdam, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Lubberts","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Erasmus MC, University Medical Center","place":["Rotterdam, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2015.53","article-title":"The il-23-il-17 axis in inflammatory arthritis","volume":"11","author":"Lubberts","year":"2015","journal-title":"Nat Rev Rheumatol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1331217","article-title":"Il-23 past, present, and future: a roadmap to 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