{
  "abstract": "The cytokine interleukin-6 orchestrates inflammation through two distinct pathways of receptor activation: anti-inflammatory classic signalling via membrane-bound interleukin-6 receptor and pro-inflammatory trans-signalling via soluble interleukin-6 receptor. Current interleukin-6-targeted therapies block both pathways, thereby disrupting essential homeostatic functions initiated by classic signalling. We here show a high-affinity, human-specific antibody that selectively inhibits interleukin-6 trans-signalling. This antibody maintains classic signalling-induced expression of hepatic acute phase genes while completely blocking trans-signalling-induced activation of endothelial cells. By targeting the domain D2 of membrane-bound and soluble human interleukin-6 receptor, the antibody selectively prevents formation of the trans-signalling receptor complex without interfering with ligand binding. This selective blockade demonstrates that human interleukin-6 classic and trans-signalling proceed through distinct receptor assemblies. Our findings describe mechanistic insight into interleukin-6 receptor assembly and provide a strategy to suppress inflammatory interleukin-6 activity while preserving regenerative and anti-inflammatory signalling, thus offering both conceptual and potential therapeutic advances in the targeted modulation of cytokine signalling networks.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "name": "Emelie Rieneck",
      "orcid": "0009-0005-6662-0450"
    },
    {
      "name": "Jan René Haak"
    },
    {
      "name": "Kamal Asgarov"
    },
    {
      "name": "Jean-René Pallandre"
    },
    {
      "name": "Nicole Wundrack",
      "orcid": "0000-0003-0894-8448"
    },
    {
      "name": "Julia Ettich"
    },
    {
      "name": "Niloufarsadat Miri",
      "orcid": "0000-0001-6619-9524"
    },
    {
      "name": "Doreen M. Floss",
      "orcid": "0000-0002-6675-5313"
    },
    {
      "name": "Jürgen Scheller",
      "orcid": "0000-0001-9932-1055"
    },
    {
      "name": "Christoph Garbers",
      "orcid": "0000-0003-4939-6950"
    },
    {
      "name": "Andy Clark"
    },
    {
      "name": "John Wijdenes"
    },
    {
      "name": "Fred Schaper",
      "orcid": "0000-0002-8899-5414"
    },
    {
      "name": "Anna Dittrich",
      "orcid": "0000-0002-1056-4219"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6p9eqkkr7v27y.bib",
  "cited_by": 0,
  "doi": "10.1038/s42003-026-11014-0",
  "fulltext_url": "https://europepmc.org/articles/PMC13669321",
  "id": "6p9eqkkr7v27y",
  "issns": [
    "2399-3642"
  ],
  "landing_url": "https://www.nature.com/articles/s42003-026-11014-0",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2730|Cytokine Signaling Pathways and Interactions"
    ]
  ],
  "openalex": "W7221812919",
  "pdf_url": "https://www.nature.com/articles/s42003-026-11014-0.pdf",
  "pmcid": "PMC13669321",
  "pmid": "42875473",
  "published": "2026-10-14",
  "publisher": "Springer Science and Business Media LLC",
  "ris": "https://research.draconitic.com/paper/6p9eqkkr7v27y.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:50Z",
      "native_id": "10.1038/s42003-026-11014-0",
      "source": "crossref",
      "url": "https://www.nature.com/articles/s42003-026-11014-0"
    },
    {
      "first_seen": "2026-10-30T12:18:46Z",
      "native_id": "MED:42875473",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42875473"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cytokine Signaling Pathways and Interactions",
      "subfield": "oncology"
    }
  ],
  "title": "Selective inhibition of IL-6 trans-signalling reveals distinct mechanisms of human classic and trans-signalling receptor-complex formation",
  "title_text": "Selective inhibition of IL-6 trans-signalling reveals distinct mechanisms of human classic and trans-signalling receptor-complex formation",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:46Z",
  "url": "https://research.draconitic.com/paper/6p9eqkkr7v27y",
  "venue": "Communications Biology",
  "versions": []
}