{
  "abstract": "Regulatory T cells (Tregs) are critical for immune tolerance. However, direct Treg therapies generate limited results. Recently, combinational treatment with Tregs and IL-2 to expand Tregs has become a hotspot and appeared to be promising. Here we unexpectedly find that infusion of CD4+CD25+ Tregs plus IL-2 in lymphocyte-deficient mice causes skin and heart allograft rejection, while IL-2 or Treg alone does not. Depletion of CD25+ Tregs in recipient mice receiving Tregs plus IL-2 abrogates allograft rejection. Gene profiling via qPCR arrays shows a tremendous increase in CXCL15 expression in allografts after the joint treatment. Its expression is augmented in Tregs from recipient mice. IL-2 augments CXCL15/IL-8 production by murine or human Tregs. Moreover, neutrophil infiltration is increased in allografts of mice receiving Tregs plus IL-2. However, allograft rejection or neutrophil infiltration does not occur when transferred Tregs lack CXCL15. Finally, the joint treatment provokes cardiac allograft rejection in pre-tolerized wild-type mice, while IL-2 or Treg alone does not. These results unveil hidden and detrimental effects of Tregs on transplant survival and somewhat challenge current dogma that Tregs are always immunosuppressive.",
  "abstract_shown": true,
  "affiliations": [
    "Section of Immunology, Guangdong Provincial Academy of Chinese Medical Sciences",
    "Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology",
    "Kidney and Pancreas Transplantation, Department of Microbiology & Immunology and Department of Surgery, University of Maryland School of Medicine"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Feifei Qiu"
    },
    {
      "affs": [
        0
      ],
      "name": "Huazhen Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Chun-Ling Liang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuchao Chen"
    },
    {
      "affs": [
        1
      ],
      "name": "Nianqiao Gong"
    },
    {
      "affs": [
        2
      ],
      "name": "Jonathan S. Bromberg"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhenhua Dai"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4js89qk0x4a5d.bib",
  "cited_by": 0,
  "doi": "10.1038/s42003-026-10542-z",
  "fulltext_url": "https://doi.org/10.1038/s42003-026-10542-z",
  "id": "4js89qk0x4a5d",
  "issns": [
    "2399-3642"
  ],
  "landing_url": "https://doi.org/10.1038/s42003-026-10542-z",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "QH301-705.5"
    ],
    [
      "openalex",
      "2403|T-cell and B-cell Immunology"
    ]
  ],
  "openalex": "W7166531206",
  "pdf_url": "https://www.nature.com/articles/s42003-026-10542-z_reference.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-06-01",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/4js89qk0x4a5d.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:46:27Z",
      "native_id": "e19364a9daec49078fe60e6390a01718",
      "source": "doaj",
      "url": "https://doi.org/10.1038/s42003-026-10542-z"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|T-cell and B-cell Immunology",
      "subfield": "immunology"
    }
  ],
  "title": "CD4+CD25+ regulatory T cells circumstantially initiate transplant rejection through CXCL15/neutrophil axis",
  "title_text": "CD4+CD25+ regulatory T cells circumstantially initiate transplant rejection through CXCL15/neutrophil axis",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:46:27Z",
  "url": "https://research.draconitic.com/paper/4js89qk0x4a5d",
  "venue": "Communications Biology",
  "versions": []
}