{
  "abstract": "Immunoproteasomes are specialized multiprotein proteases that degrade intracellular proteins. Their products serve as peptides for human leukocyte antigen class I presentation playing a key role in antiviral defense and self-tolerance. Monoallelic variants in immunoproteasome genes including proteasome subunit β type 10 have recently been associated with autoinflammatory diseases and severe combined immune deficiency. Their pathophysiological consequences remain poorly understood, and treatment options are scarce. We identified a newborn with severe T lymphopenia and a de novo dominant-negative PSMB10 p.G209R mutation after pathological T cell receptor excision circle newborn screening. We further applied molecular modeling, proteomics, transcriptomics, and ex vivo T lymphopoiesis. Simulations predicted, and biochemical studies confirmed, impaired immunoproteasome assembly and function leading to defective viral sensing and antigen presentation signatures in interferon-treated fibroblasts. Despite this, hematopoietic stem cells differentiated into T cells ex vivo, and the patient developed normal naïve T cell counts and a diverse T cell antigen receptor repertoire within the first year of life in contrast to all previously reported patients.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 25,
  "authors": [
    {
      "name": "Sujal Ghosh"
    },
    {
      "name": "Yuqin Wang"
    },
    {
      "name": "Christoph Schultheiss"
    },
    {
      "name": "Arndt Borkhardt"
    },
    {
      "name": "Angelique Sanchez Dafun"
    },
    {
      "name": "Liisa Knipp"
    },
    {
      "name": "Sebastian Marwitz"
    },
    {
      "name": "Stephan Ehl"
    },
    {
      "name": "Clara Soulard"
    },
    {
      "name": "Elie Haddad"
    },
    {
      "name": "Debayan Dey"
    },
    {
      "name": "Grace Evans"
    },
    {
      "name": "Zainab M Golwala"
    },
    {
      "name": "Sabrina B Bennstein"
    },
    {
      "name": "Hans-Jürgen Laws"
    },
    {
      "name": "Meino Rohlfs"
    },
    {
      "name": "Thomas Magg"
    },
    {
      "name": "Mascha Binder"
    },
    {
      "name": "Alexandra Y Kreins"
    },
    {
      "name": "Marie-Pierre Bousquet"
    },
    {
      "name": "Julien Marcoux"
    },
    {
      "name": "Christoph Klein"
    },
    {
      "name": "Graeme L Conn"
    },
    {
      "name": "Silke Meiners"
    },
    {
      "name": "Fabian Hauck"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/anmma4mf8rc60.bib",
  "cited_by": 3,
  "doi": "10.70962/jhi.20250129",
  "fulltext_url": null,
  "id": "anmma4mf8rc60",
  "issns": [
    "3065-8993",
    "3065-8993"
  ],
  "landing_url": "https://hal.science/hal-05844244v1",
  "language": "en",
  "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": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "hal",
      "1.sdv.bbm"
    ],
    [
      "hal",
      "1.sdv.imm"
    ],
    [
      "hal",
      "1.sdv.mhep"
    ],
    [
      "hal",
      "2.sdv.bbm.gtp"
    ],
    [
      "hal",
      "2.sdv.imm.ia"
    ],
    [
      "hal",
      "2.sdv.mhep.hem"
    ],
    [
      "openalex",
      "2403|Immunodeficiency and Autoimmune Disorders"
    ]
  ],
  "openalex": "W7153112244",
  "pdf_url": "https://hal.science/hal-05844244/document",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-29",
  "publisher": "Rockfeller university press",
  "ris": "https://research.draconitic.com/paper/anmma4mf8rc60.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:03Z",
      "native_id": "hal-05844244",
      "source": "hal",
      "url": "https://hal.science/hal-05844244v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "hal:2.sdv.bbm.gtp",
      "subfield": "proteomics-metabolomics"
    },
    {
      "field": "biology",
      "origin": "hal:1.sdv.imm",
      "subfield": "immunology"
    },
    {
      "field": "medicine",
      "origin": "hal:1.sdv.mhep",
      "subfield": "general"
    }
  ],
  "title": "Dominant-negative PSMB10 disrupts immunoproteasome assembly and leads to transient T lymphopenia",
  "title_text": "Dominant-negative PSMB10 disrupts immunoproteasome assembly and leads to transient T lymphopenia",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:20:56Z",
  "url": "https://research.draconitic.com/paper/anmma4mf8rc60",
  "venue": "Journal of Human Immunity",
  "versions": []
}