{
  "abstract": "In immune thrombocytopenia (ITP), an autoimmune bleeding disorder, macrophages serve as key effector cells that mediate platelet clearance and sustain immune dysregulation. Signal transducer and activator of transcription 1 (STAT1) regulates inflammatory macrophage activation, whereas mitochondrial quality control shapes macrophage function by maintaining mitochondrial homeostasis. Although STAT1-associated signaling and mitochondrial quality control both influence macrophage function, their functional relationship in ITP remains unclear. Here, we used 2-bromopalmitate (2-BP), a broad-spectrum pharmacological probe that perturbs the S-acylation cycle, to examine STAT1-associated signaling, mitochondrial quality control, and macrophage function in experimental ITP. In inflammatory macrophages, 2-BP treatment was associated with reduced hydroxylamine-sensitive STAT1 S-acylation, decreased STAT1 Tyr701 phosphorylation and nuclear accumulation, restored mitochondrial membrane potential, reduced cellular and mitochondrial reactive oxygen species, and increased PINK1/Parkin-associated mitochondrial quality-control markers. These changes were accompanied by a shift from an M1-like inflammatory phenotype toward an M2-like immunoregulatory phenotype, reduced pro-inflammatory cytokine production, and lower particle uptake. STAT1 overexpression attenuated the 2-BP-associated improvements in mitochondrial quality-control markers, mitochondrial membrane potential, reactive oxygen species, and macrophage phenotype. In a passive mouse model of ITP, 2-BP treatment was associated with improved platelet recovery, ameliorated splenic histopathological changes, reduced macrophage-associated CD41 signals in the spleen, and an increased proportion of M2-like splenic macrophages. These 2-BP-associated in vivo changes were attenuated in the 2-BP/Mdivi-1 co-treatment group. Collectively, these findings identify concurrent 2-BP-associated changes in STAT1 S-acylation and activation, mitochondrial quality control, and macrophage function. They support STAT1 signaling as an important functional contributor to the effects of 2-BP on macrophage reprogramming and mitochondrial homeostasis in experimental ITP. These findings provide mechanistic insight into the regulation of macrophage function in experimental ITP and support further investigation of more selective strategies targeting macrophage inflammatory signaling and mitochondrial quality control.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Original Research",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "name": "Xiaoyuan Fan"
    },
    {
      "name": "Mingwei Li"
    },
    {
      "name": "Danlu Li"
    },
    {
      "name": "Li Cao"
    },
    {
      "name": "Mei Yan"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dxabdxnvxgzvc.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.2004045",
  "fulltext_url": null,
  "id": "dxabdxnvxgzvc",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.2004045",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "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": "2026-11-10",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/dxabdxnvxgzvc.ris",
  "sources": [
    {
      "first_seen": "2026-11-10T12:20:56Z",
      "native_id": "10.3389/fimmu.2026.2004045",
      "source": "feed-frontiers",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.2004045"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "feed-journal:biology/immunology",
      "subfield": "immunology"
    }
  ],
  "title": "2-bromopalmitate modulates macrophage polarization and mitophagy through STAT1-associated signaling in immune thrombocytopenia",
  "title_text": "2-bromopalmitate modulates macrophage polarization and mitophagy through STAT1-associated signaling in immune thrombocytopenia",
  "type": "peer-reviewed",
  "updated_at": "2026-11-10T12:20:56Z",
  "url": "https://research.draconitic.com/paper/dxabdxnvxgzvc",
  "venue": "Frontiers in Immunology",
  "versions": []
}