{
  "abstract": "The hyperinflammatory syndromes in patients who are critically ill, including those with trauma injury, sepsis, and acute lung injury, are characterized by dysregulated neutrophil responses that contribute to tissue damage and poor outcomes. Using murine models of cytokine storm induced by trauma and lung injury, we identified transforming growth factor β (TGF-β) as a central regulator of immune checkpoints in neutrophils. TGF-β signaling modulates neutrophil activation and upregulates the expression of programmed death-ligand 1 (PDL1). Disruption of TGF-β signaling during hyperinflammation restores the migratory capacity of neutrophils but leads to excessive activation, severe pulmonary tissue damage, and increased susceptibility to spontaneous bacterial infection in the lung. Mechanistically, PDL1 expression alters neutrophil behavior within lung capillaries, promoting intravascular clustering and restricting tissue infiltration. Targeted deletion of PDL1 in neutrophils reverses hyperinflammation-induced clustering, restores effective trafficking to infectious foci, and enhances host-protective immune function while limiting pathological neutrophil hyperactivation. These findings define a TGF-β–PDL1 regulatory axis that restrains the pathogenicity of neutrophils during hyperinflammation, revealing a checkpoint mechanism that balances host defense and tissue integrity.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada",
    "Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA",
    "Division of Pulmonary, Allergy and Critical Care Medicine, Stanford University, Stanford, CA",
    "Division of Computational Medicine, Department of Medicine, Stanford University, Stanford, CA",
    "Department of Physiology, McGill University, Montreal, QC, Canada",
    "Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China",
    "Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada",
    "Meakins-Christie Laboratories, Research Institute of the McGill University Health Centre, Montreal, QC, Canada",
    "Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada",
    "Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada",
    "Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden",
    "Vaccine and Immune Therapies, BioPharmaceuticals Research & Development Center, AstraZeneca, Gaithersburg, MD",
    "Department of Bioengineering, McGill University, Montreal, QC, Canada"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 24,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Ziyi Li"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Andrew R. Moore"
    },
    {
      "affs": [
        1,
        3
      ],
      "name": "Hong Zheng"
    },
    {
      "affs": [
        0
      ],
      "name": "Janmes Karunamurthy"
    },
    {
      "affs": [
        4
      ],
      "name": "Aanya Bhagrath"
    },
    {
      "affs": [
        5
      ],
      "name": "Jiangxue Li"
    },
    {
      "affs": [
        6
      ],
      "name": "Daniel Young"
    },
    {
      "affs": [
        7
      ],
      "name": "Leonardo F. Jurado"
    },
    {
      "affs": [
        0
      ],
      "name": "Katalina Couto"
    },
    {
      "affs": [
        8
      ],
      "name": "Amelia Kulle"
    },
    {
      "affs": [
        0
      ],
      "name": "Haley Park"
    },
    {
      "affs": [
        0
      ],
      "name": "Ashley Kwak"
    },
    {
      "affs": [
        0
      ],
      "name": "Vaishnav Belur"
    },
    {
      "affs": [
        9,
        10
      ],
      "name": "Sebastien Talbot"
    },
    {
      "affs": [
        7
      ],
      "name": "Maziar Divangahi"
    },
    {
      "affs": [
        11
      ],
      "name": "Antonio DiGiandomenico"
    },
    {
      "affs": [
        2
      ],
      "name": "Angela Rogers"
    },
    {
      "affs": [
        11
      ],
      "name": "Taylor S. Cohen"
    },
    {
      "affs": [
        12
      ],
      "name": "Allen J. Ehrlicher"
    },
    {
      "affs": [
        4
      ],
      "name": "Judith N. Mandl"
    },
    {
      "affs": [
        5
      ],
      "name": "Jing Wang"
    },
    {
      "affs": [
        6
      ],
      "name": "Antoine Dufour"
    },
    {
      "affs": [
        1,
        3
      ],
      "name": "Purvesh Khatri"
    },
    {
      "affs": [
        0,
        8
      ],
      "name": "Ajitha Thanabalasuriar"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e4emqxwherpcx.bib",
  "cited_by": 1,
  "doi": "10.1182/blood.2025031635",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13721869/",
  "id": "e4emqxwherpcx",
  "issns": [
    "0006-4971",
    "1528-0020"
  ],
  "landing_url": "https://doi.org/10.1182/blood.2025031635",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Phagocytes, Granulocytes, and Myelopoiesis"
    ],
    [
      "openalex",
      "2403|Inflammation biomarkers and pathways"
    ]
  ],
  "openalex": "W7161690552",
  "pdf_url": "https://ashpublications.org/blood/article-pdf/148/15/1925/2593047/blood_bld-2025-031635-main.pdf",
  "pmcid": "PMC13721869",
  "pmid": "42154905",
  "published": "2026-05-22",
  "publisher": "The American Society of Hematology",
  "ris": "https://research.draconitic.com/paper/e4emqxwherpcx.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T12:22:29Z",
      "native_id": "PMC13721869",
      "source": "pmc",
      "url": "https://doi.org/10.1182/blood.2025031635"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Inflammation biomarkers and pathways",
      "subfield": "immunology"
    }
  ],
  "title": "TGF-β–PDL1 signaling in neutrophils preserves the lung barrier during hyperinflammation",
  "title_text": "TGF-β–PDL1 signaling in neutrophils preserves the lung barrier during hyperinflammation",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:22:29Z",
  "url": "https://research.draconitic.com/paper/e4emqxwherpcx",
  "venue": "Blood",
  "versions": []
}