{
  "abstract": "Inflammatory responses are heterogeneous, even among cells exposed to a common insult, yet the regulatory mechanisms that distinguish these inflammatory states remain poorly understood. Here, we leveraged inflammatory state heterogeneity to identify a conserved Foxp1-Pde4d regulatory relationship and uncover a role for this axis in preserving inflammatory responsiveness. Genotoxic stress in adipocyte progenitors generated heterogeneous engagement of type-I interferon (IFN) and NF{kappa}B transcriptional programmes, and transcriptome-wide analysis independently identified Foxp1 and the cAMP phosphodiesterase Pde4d among genes associated with lower IFN- and higher NF{kappa}B-associated transcription. ChIP-seq revealed selective loss of Foxp1 occupancy at a Pde4d-associated regulatory element following genotoxic stress, while Foxp1 gain- and loss-of-function established Foxp1 as a positive regulator of Pde4d expression. Remarkably, coupling of Foxp1-Pde4d expression was broadly conserved across vertebrate tissues and damage models. In vivo, Foxp1 loss in zebrafish revealed a striking dissociation between inflammatory state and response capacity: basal NF{kappa}B activity was elevated, yet injury-induced NF{kappa}B activation was markedly blunted and macrophage recruitment impaired. Adenylyl cyclase inhibition restored macrophage recruitment in Foxp1-deficient zebrafish, functionally linking the Foxp1 phenotype to cAMP signalling and supporting a model in which Foxp1-Pde4d regulation preserves inflammatory responsiveness through control of cAMP. Together, these findings show how inflammatory-state heterogeneity can reveal conserved regulatory mechanisms linking basal cellular state to subsequent response capacity.",
  "abstract_shown": true,
  "affiliations": [
    "Institute for Neuroscience and Cardiovascular Research, University of Edinburgh"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "name": "L. M. Elemans"
    },
    {
      "name": "P. Tandon"
    },
    {
      "name": "G. Rodger"
    },
    {
      "name": "L. Stirling"
    },
    {
      "name": "S. Hendry"
    },
    {
      "name": "M. N. Akhtar"
    },
    {
      "name": "X. Chen"
    },
    {
      "name": "T. Mitic"
    },
    {
      "name": "Y. Feng"
    },
    {
      "name": "R. K. Semple"
    },
    {
      "affs": [
        0
      ],
      "name": "J. E. Minchin"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cftds27b7210e.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.27.762160",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.27.762160v1.full",
  "id": "cftds27b7210e",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.27.762160v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cell biology"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.27.762160v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-27",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/cftds27b7210e.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:21:20Z",
      "native_id": "10.64898/2026.10.27.762160",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.27.762160v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:cell biology",
      "subfield": "cell-biology"
    }
  ],
  "title": "A conserved Foxp1-Pde4d axis regulates inflammatory responsiveness",
  "title_text": "A conserved Foxp1-Pde4d axis regulates inflammatory responsiveness",
  "type": "preprint",
  "updated_at": "2026-11-01T00:21:15Z",
  "url": "https://research.draconitic.com/paper/cftds27b7210e",
  "venue": "bioRxiv",
  "versions": []
}