{
  "abstract": "Inflammatory hemophagocytes (iHPCs) differentiate from Ly6CHI monocytes, phagocytose red blood cells, and promote anemia and thrombocytopenia in a model of TLR7-driven macrophage activation syndrome (MAS), a life-threatening disorder. We identify IRF5 as a required and pharmacologically targetable driver of iHPC differentiation and MAS pathogenesis. Ly6CHI monocyte-to-iHPC differentiation in TLR7.1 mice involved extensive transcriptome and chromatin remodeling. Gene programs gained in iHPCs were enriched for genes near accessible IRF5-binding regions that also carried NF-{kappa}B, ETS, and AP-1 motifs, suggesting collaborative regulation. IRF5 was required in vitro for TLR7-induced upregulation of a subset of these genes. Cell-intrinsic IRF5 expression was required for iHPC differentiation but dispensable for TLR7.1 Ly6CHI monocytes and their transcriptional programs. Constitutive and myeloid-specific Irf5 deletion, as well as a small-molecule IRF5 inhibitor, reduced iHPCs and ameliorated MAS and lupus features. IRF5 is therefore a broad regulator of iHPC differentiation and a tractable target in TLR7-driven inflammation.",
  "abstract_shown": true,
  "affiliations": [
    "Benaroya Research Institute"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "name": "N. K. Thulin"
    },
    {
      "name": "A. Lu"
    },
    {
      "name": "S. L. Orozco"
    },
    {
      "name": "A. Y. Y. Huang"
    },
    {
      "name": "L. P. Nguyen"
    },
    {
      "name": "G. Mishra"
    },
    {
      "name": "R. Savan"
    },
    {
      "name": "W. Clapp"
    },
    {
      "name": "J. Ray"
    },
    {
      "affs": [
        0
      ],
      "name": "J. Hamerman"
    },
    {
      "name": "B. J. Barnes"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/b93mqr1yag4pe.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.08.18.745337",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.08.18.745337v2.full",
  "id": "b93mqr1yag4pe",
  "issns": [
    "2692-8205"
  ],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.08.18.745337v2",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "immunology"
    ],
    [
      "openalex",
      "2720|Autoimmune and Inflammatory Disorders Research"
    ]
  ],
  "openalex": "W7204096780",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.08.18.745337v2.full.pdf",
  "pmcid": "PMC13742588",
  "pmid": null,
  "published": "2026-08-18",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/b93mqr1yag4pe.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:28:06Z",
      "native_id": "10.64898/2026.08.18.745337",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.08.18.745337v2"
    },
    {
      "first_seen": "2026-11-09T15:20:34Z",
      "native_id": "PMC:PMC13742588",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13742588"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Myeloid IRF5 is required for TLR7-driven inflammatory hemophagocyte differentiation and Macrophage Activation Syndrome",
  "title_text": "Myeloid IRF5 is required for TLR7-driven inflammatory hemophagocyte differentiation and Macrophage Activation Syndrome",
  "type": "preprint",
  "updated_at": "2026-11-09T15:20:34Z",
  "url": "https://research.draconitic.com/paper/b93mqr1yag4pe",
  "venue": "bioRxiv",
  "versions": []
}