{
  "abstract": "IntroductionDecidual macrophages participate in the inflammatory processes associated with parturition. However, the potential relationship between iron availability and macrophage inflammatory regulation at the maternal–fetal interface remains incompletely understood. This study aimed to investigate the association between iron status and decidual macrophage phenotypes during term labor and to explore the potential involvement of transferrin receptor 1 (TfR1)/Toll-like receptor 4 (TLR4)-associated signaling.MethodsHuman decidual tissues obtained from women at term labor (TL) and term not in labor (TNL) were analyzed for total iron content, macrophage phenotypic markers, and TfR1 and TLR4 expression. A graded dietary iron supplementation mouse model was used to examine the relationship between iron availability, decidual macrophage phenotypes, and TfR1/TLR4 expression at labor onset. In vitro experiments using RAW264.7 macrophages, iron manipulation, and siRNA-mediated knockdown of TfR1 and TLR4 were performed to investigate their potential regulatory relationships.ResultsCompared with TNL tissues, TL decidual tissues exhibited significantly higher total iron content, increased CD68+CD86+ and decreased CD68+CD206+ macrophage populations, accompanied by enhanced TfR1 and TLR4 expression. In pregnant mice, increasing dietary iron concentrations were associated with greater expression of M1-associated macrophage markers and increased TfR1/TLR4 expression in decidual tissues, without significant changes in maternal hematological parameters. In vitro, ferric ammonium citrate (FAC) enhanced M1-associated macrophage phenotypes and inflammatory cytokine expression, whereas deferoxamine (DFO) attenuated these responses. TfR1 knockdown reduced TLR4 expression, MyD88/NF-κB-associated signaling, and inflammatory responses. Conversely, TLR4 knockdown attenuated macrophage inflammatory activation without significantly altering TfR1 expression. These findings are consistent with a potential regulatory relationship between TfR1 and TLR4-associated signaling under the experimental conditions examined.DiscussionIncreased decidual iron content, enhanced expression of M1-associated macrophage markers, and elevated TfR1/TLR4 expression were observed concomitantly during term labor. Complementary animal and cell experiments suggest that iron availability may contribute to macrophage inflammatory regulation, potentially involving TfR1/TLR4/MyD88/NF-κB-associated signaling. These findings provide insights into the potential interplay between iron availability and innate immune responses at the maternal–fetal interface, although further studies are needed to establish the physiological relevance of this mechanism during human labor.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Original Research",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "name": "Xiaoying Wang"
    },
    {
      "name": "Wenjia Lan"
    },
    {
      "name": "Limin Song"
    },
    {
      "name": "Xuemei Piao"
    },
    {
      "name": "Yan Cai"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/f6e9qb5f4ajsj.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1897445",
  "fulltext_url": null,
  "id": "f6e9qb5f4ajsj",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1897445",
  "language": null,
  "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": [
    [
      "feed-journal",
      "biology/immunology"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-05",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/f6e9qb5f4ajsj.ris",
  "sources": [
    {
      "first_seen": "2026-11-05T06:20:17Z",
      "native_id": "10.3389/fimmu.2026.1897445",
      "source": "feed-frontiers",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1897445"
    },
    {
      "first_seen": "2026-11-05T12:21:11Z",
      "native_id": "10.3389/fimmu.2026.1897445",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1897445/full"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "feed-journal:biology/immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Iron promotes M1 polarization of decidual macrophages during parturition via increased TfR1 and TLR4 expression",
  "title_text": "Iron promotes M1 polarization of decidual macrophages during parturition via increased TfR1 and TLR4 expression",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T00:21:16Z",
  "url": "https://research.draconitic.com/paper/f6e9qb5f4ajsj",
  "venue": "Frontiers in Immunology",
  "versions": []
}