{
  "abstract": "Mutations in human FERMT3 (encoding kindlin-3 protein) impair β2 integrin activity in neutrophils from patients with leukocyte adhesion deficiency III (LAD-III). Yet kindlin-3's contribution to neutrophil integrin affinity regulation and function remains unclear. Using CD34+ human hematopoietic stem and progenitor cells (HSPCs) differentiated into neutrophils, we investigated how CRISPR/Cas9-mediated kindlin-3 deletion affects neutrophil characteristics. CRISPR/Cas9 targeting FERMT3 resulted in an ∼80-bp deletion within exon 2, impairing protein production. FERMT3 KO neutrophils retained normal in vitro development and phenotype with similar surface marker expression, nuclear morphology, and expansion potential compared with untreated cultured neutrophils. Loss of kindlin-3 abolished zymosan-induced NADPH oxidase activity, recapitulating the ROS production defect of LAD-III neutrophils. However, although basal adhesion was reduced, stimulus-induced integrin activity remained largely intact. FERMT3 KO neutrophils retained fMLP-driven chemotaxis while showing impaired migration in response to C5a. Together, these findings show that disruption of kindlin-3 largely recapitulates the LAD-III phenotype while exerting some effector functions upon stimulation without intact kindlin-3.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Research, Sanquin Blood Supply Foundation, Amsterdam, Netherlands.",
    "Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.",
    "Department of Molecular and Integrative Biosciences, Faculty of Biological and Environmental Sciences, University of Helsinki, Helsinki, Finland.",
    "Institute of Molecular Oncology and Functional Genomics, School of Medicine, Technical University of Munich , Munich, Germany.",
    "Institute of Experimental Hematology School of Medicine and Health, Technical University of Munich , Munich, Germany.",
    "Center for Translational Cancer Research (TranslaTUM), School of Medicine and Health, Technical University of Munich , Munich, Germany.",
    "Department of Pediatric Immunology, Rheumatology & Infectious Diseases, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Steven D S Webbers",
      "orcid": "0000-0003-1064-0776"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Felipe Rojas-Rodriguez",
      "orcid": "0000-0003-2159-7224"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Angela A F Gankema",
      "orcid": "0000-0001-7073-9677"
    },
    {
      "affs": [
        2
      ],
      "name": "Imran Khan",
      "orcid": "0000-0002-9892-7271"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Judy Geissler",
      "orcid": "0000-0002-2645-1008"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Anton T J Tool",
      "orcid": "0000-0002-8227-1888"
    },
    {
      "affs": [
        3
      ],
      "name": "Rupert Öllinger",
      "orcid": "0000-0002-2292-5982"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Robin van Bruggen",
      "orcid": "0000-0002-1676-0720"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Teunis J P van Dam",
      "orcid": "0000-0002-8122-190X"
    },
    {
      "affs": [
        2
      ],
      "name": "Suzanna C Fagerholm",
      "orcid": "0000-0002-0354-8763"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Markus Moser",
      "orcid": "0000-0001-8825-5566"
    },
    {
      "affs": [
        0,
        1,
        6
      ],
      "name": "Taco W Kuijpers",
      "orcid": "0000-0002-7421-3370"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bpy3p59qnwnf7.bib",
  "cited_by": 0,
  "doi": "10.70962/jhi.20260086",
  "fulltext_url": "https://europepmc.org/articles/PMC13685712",
  "id": "bpy3p59qnwnf7",
  "issns": [
    "3065-8993"
  ],
  "landing_url": "https://europepmc.org/article/MED/42905029",
  "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|Immunodeficiency and Autoimmune Disorders"
    ]
  ],
  "openalex": "W7223108903",
  "pdf_url": "https://europepmc.org/articles/PMC13685712?pdf=render",
  "pmcid": "PMC13685712",
  "pmid": "42905029",
  "published": "2026-10-21",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/bpy3p59qnwnf7.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:53Z",
      "native_id": "MED:42905029",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42905029"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Immunodeficiency and Autoimmune Disorders",
      "subfield": "immunology"
    }
  ],
  "title": "CRISPR/Cas9-mediated loss of FERMT3 reveals kindlin-3-independent neutrophil activity in LAD-III.",
  "title_text": "CRISPR/Cas9-mediated loss of FERMT3 reveals kindlin-3-independent neutrophil activity in LAD-III.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:53Z",
  "url": "https://research.draconitic.com/paper/bpy3p59qnwnf7",
  "venue": "Journal of human immunity",
  "versions": []
}