{
  "abstract": "Type 1 diabetes (T1D) is driven by immune-mediated destruction and dysfunction of pancreatic β-cells, with autoreactive CD8+ T cells serving as important effectors of β-cell injury. T-cell immunoglobulin and mucin domain-containing protein 4 (TIM-4) is expressed predominantly by macrophages and subsets of antigen-presenting cells and participates in phosphatidylserine recognition, efferocytosis, and regulation of adaptive immune responses. We investigated whether short-course TIM-4 targeting alters diabetogenic antigen-specific CD8+ T-cell responses in female non-obese diabetic (NOD) mice with new-onset diabetes. Mice received an anti-TIM-4 monoclonal antibody (3 mg/kg, intraperitoneally, every 2 days for 4 doses). Autoreactive CD8+ T cells were quantified using H-2Kd tetramers loaded with an insulin peptide or the islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)206–214 peptide, and pancreatic histology and intracellular interferon-γ (IFN-γ), interleukin-17 (IL-17), and forkhead box P3 (FoxP3) staining were assessed. Euglycemia was restored in 8 of 11 treated mice (72.7%) despite cessation of therapy. Anti-TIM-4 monoclonal antibody treatment markedly reduced IGRP206–214-reactive CD8+ T-cell frequencies in pancreatic lymph nodes and pancreas compared with untreated diabetic mice and was associated with preservation of pancreatic islet architecture. Treatment was also associated with lower IFN-γ and IL-17 expression and a higher frequency of FoxP3+ CD4+ T cells in pancreatic lymph nodes. These findings identify TIM-4-associated immune pathways as potential modulators of diabetogenic antigen-specific CD8+ T-cell responses and support further mechanistic evaluation of TIM-4 targeting in autoimmune diabetes.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Nephrology, Department of Internal Medicine, School of Medicine, Kyungpook National University Hospital, Kyungpook National University, Daegu 41944, Republic of Korea",
    "Cell and Matrix Research Institute, Kyungpook National University, Daegu 41944, Republic of Korea"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yoon-Ju Kim"
    },
    {
      "affs": [
        0
      ],
      "name": "You Hyun Jeon",
      "orcid": "0000-0001-7318-5753"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Se-Hyun Oh"
    },
    {
      "affs": [
        0
      ],
      "name": "Yu-Kyung Chung"
    },
    {
      "affs": [
        0
      ],
      "name": "Hee-Yeon Jung"
    },
    {
      "affs": [
        0
      ],
      "name": "Ji-Young Choi"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Jang-Hee Cho",
      "orcid": "0000-0002-7031-5214"
    },
    {
      "affs": [
        0
      ],
      "name": "Sun-Hee Park",
      "orcid": "0000-0002-0953-3343"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Chan-Duck Kim",
      "orcid": "0000-0002-4648-0324"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/175a8tsapfmbc.bib",
  "cited_by": 0,
  "doi": "10.3390/biom16101498",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13702673/?tool=EBI",
  "id": "175a8tsapfmbc",
  "issns": [
    "2218-273X"
  ],
  "landing_url": "https://www.mdpi.com/2218-273X/16/10/1498",
  "language": "eng",
  "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": [
    [
      "openalex",
      "1311|Diabetes and associated disorders"
    ]
  ],
  "openalex": "W7221794373",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13702673/pdf/?tool=EBI",
  "pmcid": "PMC13702673",
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/175a8tsapfmbc.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:59Z",
      "native_id": "10.3390/biom16101498",
      "source": "crossref",
      "url": "https://www.mdpi.com/2218-273X/16/10/1498"
    },
    {
      "first_seen": "2026-10-30T12:21:44Z",
      "native_id": "PMC:PMC13702673",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13702673"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1311|Diabetes and associated disorders",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Anti-TIM-4 Monoclonal Antibody Treatment Reduces Autoreactive CD8+ T Cells and Restores Euglycemia in New-Onset Diabetic NOD Mice",
  "title_text": "Anti-TIM-4 Monoclonal Antibody Treatment Reduces Autoreactive CD8+ T Cells and Restores Euglycemia in New-Onset Diabetic NOD Mice",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:44Z",
  "url": "https://research.draconitic.com/paper/175a8tsapfmbc",
  "venue": "Biomolecules",
  "versions": []
}