{
  "abstract": "Introduction: IL-23–targeted therapies have demonstrated clinical efficacy in psoriatic arthritis (PsA), primarily through the reduction of IL-17A–driven inflammation. Consequently, most studies have focused on classical, high IL-17A-producing, CCR6 ⁺ CXCR3 ⁻ CCR4 ⁺ Th17 cells. In contrast, the impact of IL‑23 signaling on CCR6 ⁺ CXCR3 ⁺ CCR4 ⁻ Th17.1 cells —traditionally characterized by high IFN-γ and low IL-17A production—remains 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\nMethods: 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-γ secretion. Additionally, human memory CCR6 ⁻ Th1, CCR6 ⁺ Th17.1 and CCR6+ Th17 cells from healthy donors were sorted and analyzed ex vivo for IL23R , TBX21 and RORC 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-γ secretion.\n\nResults: As expected, IL-23 stimulation induced IL-17A in PsA PBMCs, whereas IL-23 inhibition reduced IL-17A secretion but did not affect IFN-γ. In healthy donor PBMCs, ex vivo IL-23R expression was restricted to memory CCR6 ⁺ Th17 and Th17.1 cells. Remarkably, IL-23 stimulation of Th17.1 cells significantly increased IFN-γ without affecting IL-17A secretion. Compared to monoculture, cocultures with monocytes increased IFN-γ 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-γ in Th17.1 cells. In contrast, IL-23 inhibition reduced IL-17A secretion in Th17 and Th17.1 cells without affecting IFN-γ production.\n\nConclusion: IL-23 exerts distinct effects on Th17.1 compared to Th17 cells. We show a role for IL-23 in IFN-γ 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 high IFN-γ high 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 high IFN-γ high Th17.1 cells.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Rheumatology, Erasmus MC, University Medical Center , ,",
    "Department of Immunology, Erasmus MC, University Medical Center , ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Bennie van Heeswijk"
    },
    {
      "affs": [
        0
      ],
      "name": "Wida Razawy"
    },
    {
      "affs": [
        0
      ],
      "name": "Nadine Davelaar"
    },
    {
      "affs": [
        0
      ],
      "name": "Anne-Marie M.C. Mus"
    },
    {
      "affs": [
        0
      ],
      "name": "Patrick S. Asmawidjaja"
    },
    {
      "affs": [
        1
      ],
      "name": "Pieter J.M. Leenen"
    },
    {
      "affs": [
        0
      ],
      "name": "Erik Lubberts"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ek8bnhy9xtjpa.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1793184",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661559/?tool=EBI",
  "id": "ek8bnhy9xtjpa",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13661559",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2403|Psoriasis: Treatment and Pathogenesis"
    ]
  ],
  "openalex": "W7214925117",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661559/pdf/?tool=EBI",
  "pmcid": "PMC13661559",
  "pmid": null,
  "published": "2026-09-30",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/ek8bnhy9xtjpa.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:21Z",
      "native_id": "PMC:PMC13661559",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13661559"
    },
    {
      "first_seen": "2026-10-30T12:19:15Z",
      "native_id": "10.3389/fimmu.2026.1793184",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1793184/full"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Psoriasis: Treatment and Pathogenesis",
      "subfield": "immunology"
    }
  ],
  "title": "IL-23 and monocyte interactions redirect human Th17.1 cells to an IL-17AhighIFN-γhigh potentially pathogenic profile",
  "title_text": "IL-23 and monocyte interactions redirect human Th17.1 cells to an IL-17AhighIFN-γhigh potentially pathogenic profile",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:15Z",
  "url": "https://research.draconitic.com/paper/ek8bnhy9xtjpa",
  "venue": "Frontiers in immunology",
  "versions": []
}