{
  "abstract": "Interleukin-21 receptor engagement initiates a Janus kinase-signal transducer and activator of transcription (STAT) signalling cascade that activates several STAT proteins that drive the germinal centre (GC) response. However, the relative effects of IL-21 on individual STAT proteins during the differentiation of T follicular helper (Tfh) cells and GC B cells has been difficult to distinguish. Here, we characterize a novel mutation in the interleukin-21 receptor (IL-21REINS) that creates a dominant defect in the activation of STAT1. Our findings provide evidence that IL-21-mediated activation of STAT1 has a non-redundant role in the differentiation of Tfh cells following T-dependent immunization. IL-21REINS Tfh cells were even more impaired than Tfh cells genetically deficient in IL-21R, questioning our current understanding of the role of IL-21 derived from protein knockout mice. The observation that functional compensation fails in the presence of the IL-21R hypomorph provides insight into how underlying compensation can impact our interpretation of a complex biological system.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Immunology, Garvan Institute of Medical Research, Darlinghurst, Australia.",
    "School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Christoph Jandl"
    },
    {
      "affs": [
        0
      ],
      "name": "Joanna Warren"
    },
    {
      "affs": [
        1
      ],
      "name": "Samantha Owens",
      "orcid": "0000-0001-6661-4150"
    },
    {
      "affs": [
        0
      ],
      "name": "Marcel Batten"
    },
    {
      "affs": [
        1
      ],
      "name": "Howard Wang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Cecile King",
      "orcid": "0000-0003-2193-2563"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e0n2y1sd9r46j.bib",
  "cited_by": 0,
  "doi": "10.7554/elife.109834",
  "fulltext_url": "https://europepmc.org/articles/PMC13694099",
  "id": "e0n2y1sd9r46j",
  "issns": [
    "2050-084X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42909478",
  "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": [
    [
      "lcc",
      "Q"
    ],
    [
      "lcc",
      "QH301-705.5"
    ],
    [
      "lcc",
      "R"
    ],
    [
      "openalex",
      "2730|Cytokine Signaling Pathways and Interactions"
    ]
  ],
  "openalex": "W7128172324",
  "pdf_url": "https://europepmc.org/articles/PMC13694099?pdf=render",
  "pmcid": "PMC13694099",
  "pmid": "42909478",
  "published": "2026-10-23",
  "publisher": "eLife Sciences Publications Ltd",
  "ris": "https://research.draconitic.com/paper/e0n2y1sd9r46j.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:03Z",
      "native_id": "MED:42909478",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42909478"
    },
    {
      "first_seen": "2026-10-30T13:44:08Z",
      "native_id": "8e6563de55ec480ca51eea380641811d",
      "source": "doaj",
      "url": "https://doi.org/10.7554/elife.109834"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cytokine Signaling Pathways and Interactions",
      "subfield": "oncology"
    }
  ],
  "title": "An IL-21R STAT hypomorph circumvents functional redundancy in germinal centre responses.",
  "title_text": "An IL-21R STAT hypomorph circumvents functional redundancy in germinal centre responses.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:44:08Z",
  "url": "https://research.draconitic.com/paper/e0n2y1sd9r46j",
  "venue": "ELife",
  "versions": []
}