{
  "abstract": "Sepsis is a serious disease associated with macrophage polarization and endothelial permeability. The DAG/PKC/ROS pathway is crucial for sepsis development, macrophage polarization and endothelial permeability. As CD4+T cell-derived exosomes can modulate the DAG/PKC/ROS pathway, we aimed to investigate the role and mechanism of exosomes from DGKK-knockdown CD4+T cells in sepsis. RAW264.7 cells were exposed to lipopolysaccharide and interferon-gamma (L/I) to promote M1 polarization and then co-cultured with exosomes. The macrophages were co-cultured with lipopolysaccharide-stimulated PMVECs. Additionally, phorbol 12-myristate 13-acetate (PMA), a PKC agonist, was used to treat macrophages. Furthermore, sepsis mouse models were established via cecal ligation and puncture (CLP) surgery. In vitro, lipopolysaccharide increased DGKK expression in CD4⁺T cells and CD4⁺T cell-derived exosomes. L/I-induced M1 macrophage polarization and DAG/PKC/ROS pathway activation were amplified by lipopolysaccharide-stimulated CD4⁺T cell exosomes. However, exosomes from DGKK-knockdown CD4⁺T cells counteracted these effects. Furthermore, treatment with these exosomes improved PMVEC viability, decreased apoptosis, alleviated inflammation, and decreased permeability. In vivo, CLP-induced inflammation, organ (lung/liver/kidney) injury, M1 macrophage polarization, DAG/PKC/ROS pathway activation, and lung permeability were further aggravated by LPS-stimulated CD4⁺T cell exosomes. However, exosomes from DGKK-knockdown CD4⁺T cells counteracted these deteriorations, while macrophage depletion abolished the protective effects of DGKK-knockdown CD4⁺T cell-derived exosomes in sepsis. Importantly, the effects of exosomes from DGKK-knockdown CD4⁺T cells on M1 macrophage polarization and endothelial permeability were reversed by PMA. In conclusion, exosomes from DGKK-knockdown CD4+T cells mitigated sepsis by suppressing the DAG/PKC/ROS pathway-mediated M1 macrophage polarization and reducing endothelial permeability, suggesting DGKK as a promising therapeutic target for sepsis.\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s10753-026-02566-8.",
  "abstract_shown": true,
  "affiliations": [
    "Department of General Practice, Affiliated Hangzhou First People’s Hospital, Westlake University School of Medicine, Hangzhou, China",
    "Department of General Practice, Affiliated Zhejiang Commercial Bank Co., Ltd., Hangzhou, China",
    "The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China",
    "Department of Emergency, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, No. 261, Huansha Road, Shangcheng District, Hangzhou City, Zhejiang Province 310006 China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Wen Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiangye Bo"
    },
    {
      "affs": [
        1
      ],
      "name": "Qianqian Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Ye Zhou"
    },
    {
      "affs": [
        2
      ],
      "name": "Nuo Zhou"
    },
    {
      "affs": [
        3
      ],
      "name": "Jinhong Wu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/758ytdq8ab5wa.bib",
  "cited_by": 0,
  "doi": "10.1007/s10753-026-02566-8",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13696612/",
  "id": "758ytdq8ab5wa",
  "issns": [
    "0360-3997",
    "1573-2576"
  ],
  "landing_url": "https://doi.org/10.1007/s10753-026-02566-8",
  "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",
      "Research"
    ],
    [
      "openalex",
      "1312|Extracellular vesicles in disease"
    ]
  ],
  "openalex": "W7171716898",
  "pdf_url": "https://europepmc.org/articles/PMC13696612?pdf=render",
  "pmcid": "PMC13696612",
  "pmid": "42928382",
  "published": "2026-07-29",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/758ytdq8ab5wa.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:56Z",
      "native_id": "PMC13696612",
      "source": "pmc",
      "url": "https://doi.org/10.1007/s10753-026-02566-8"
    },
    {
      "first_seen": "2026-10-30T12:21:20Z",
      "native_id": "MED:42928382",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42928382"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Extracellular vesicles in disease",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Exosomes from DGKK-Knockdown CD4+T Cells Alleviate Sepsis by Inhibiting the DAG/PKC/ROS Pathway-Mediated M1 Macrophage Polarization and Reducing Endothelial Permeability",
  "title_text": "Exosomes from DGKK-Knockdown CD4+T Cells Alleviate Sepsis by Inhibiting the DAG/PKC/ROS Pathway-Mediated M1 Macrophage Polarization and Reducing Endothelial Permeability",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:33:55Z",
  "url": "https://research.draconitic.com/paper/758ytdq8ab5wa",
  "venue": "Inflammation",
  "versions": []
}