{
  "abstract": "Metabolites and metabolic cofactors can shape the innate immune response, though the pathways by which these molecules adjust inflammation remain incompletely understood. Here we show that the metabolic cofactor coenzyme A (CoA) enhances IL-4 driven alternative macrophage activation [M(IL-4)] in vitro and in vivo. Unexpectedly, we find that perturbations in intracellular CoA metabolism do not influence M(IL-4) differentiation. Rather, we discover that exogenous CoA is a weak TLR4 agonist which primes macrophages for increased receptivity to IL-4 signals and resolution of inflammation via MyD88. Mechanistic studies reveal MyD88-linked signals enhance IL-4 responsiveness, in part, by reshaping chromatin accessibility to enhance transcription of IL-4-linked genes. The results identify CoA as a host metabolic co-factor that influences macrophage function through an extrinsic TLR4-dependent mechanism and suggest that damage-associated molecular patterns (DAMPs) can prime macrophages for alternative activation and resolution of inflammation.",
  "abstract_shown": true,
  "affiliations": [
    "Departments of Molecular and Medical Pharmacology, University of California",
    "Microbiology, Immunology, and Molecular Genetics, University of California",
    "Medicine, Division of Pulmonary and Critical Care Medicine; University of California"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 18,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Anthony E Jones"
    },
    {
      "affs": [
        0
      ],
      "name": "Amy Rios"
    },
    {
      "affs": [
        0
      ],
      "name": "Neira Ibrahimovic"
    },
    {
      "affs": [
        0
      ],
      "name": "Andréa B Ball"
    },
    {
      "affs": [
        0
      ],
      "name": "Carolina Chavez"
    },
    {
      "affs": [
        0
      ],
      "name": "Nicholas A Bayley"
    },
    {
      "affs": [
        0
      ],
      "name": "Natalie A Falta"
    },
    {
      "affs": [
        0
      ],
      "name": "Marisa Mekkittikul"
    },
    {
      "affs": [
        0
      ],
      "name": "Clarissa Carrillo"
    },
    {
      "affs": [
        1
      ],
      "name": "Wei Yuan Hsieh"
    },
    {
      "affs": [
        1
      ],
      "name": "Alessandro Sammarco"
    },
    {
      "affs": [
        0
      ],
      "name": "Amber B Reyes"
    },
    {
      "affs": [
        0
      ],
      "name": "Angel A Cortez"
    },
    {
      "affs": [
        0
      ],
      "name": "Thomas G Graeber"
    },
    {
      "affs": [
        2
      ],
      "name": "Richard L Watson"
    },
    {
      "affs": [
        1
      ],
      "name": "Alexander Hoffmann"
    },
    {
      "affs": [
        1
      ],
      "name": "Steven J Bensinger"
    },
    {
      "affs": [
        0
      ],
      "name": "Ajit S Divakaruni"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6z9zz1nt84pw0.bib",
  "cited_by": 0,
  "doi": "10.1038/s44319-026-00925-y",
  "fulltext_url": "https://doi.org/10.1038/s44319-026-00925-y",
  "id": "6z9zz1nt84pw0",
  "issns": [
    "1469-3178"
  ],
  "landing_url": "https://doi.org/10.1038/s44319-026-00925-y",
  "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|Immune Response and Inflammation"
    ]
  ],
  "openalex": "W7213535507",
  "pdf_url": "https://link.springer.com/content/pdf/10.1038/s44319-026-00925-y.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-01",
  "publisher": "Springer Nature",
  "ris": "https://research.draconitic.com/paper/6z9zz1nt84pw0.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:46:25Z",
      "native_id": "a9b27efd0b2e4baca96c63f2463b27a4",
      "source": "doaj",
      "url": "https://doi.org/10.1038/s44319-026-00925-y"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Immune Response and Inflammation",
      "subfield": "immunology"
    }
  ],
  "title": "Coenzyme A activates TLR4 and enhances alternative macrophage activation in line with MyD88 agonism",
  "title_text": "Coenzyme A activates TLR4 and enhances alternative macrophage activation in line with MyD88 agonism",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:46:25Z",
  "url": "https://research.draconitic.com/paper/6z9zz1nt84pw0",
  "venue": "EMBO Reports",
  "versions": []
}