{
  "abstract": "Chronic non-healing wounds are a major complication of diabetes, where persistent inflammation fails to transition into effective tissue repair (1-3). Here we identify cholinergic modulation as a mechanism that promotes productive inflammation and diabetic wound healing. Using a healing-associated fibroblast signature derived from single-cell profiling of human diabetic foot ulcers (3), we identified the acetylcholinesterase (AChE) inhibitor metrifonate as a candidate inducer of reparative wound programs. Topical delivery accelerated healing in diabetic mice and increased acetylcholine availability within the wound. Complementary receptor pharmacology identified muscarinic acetylcholine receptor 1 (CHRM1) as the principal receptor mediating the reparative response. Transcriptomic and cellular analyses revealed early induction of IL-17-associated inflammatory programs and enrichment of CHRM1NK1.1 innate lymphocytes. Depletion of NK1.1 cells or neutralization of IL-17A abolished the pro-healing effect, whereas spatial transcriptomics revealed treatment-associated organization of NK cells within vascular niches. Localized treatment further promoted repair in diabetic porcine wounds and human skin models. Together, these findings identify a CHRM1-IL-17 neuroimmune axis linking cholinergic modulation to diabetic wound repair and establish local AChE inhibition as a potential therapeutic strategy for chronic wounds.",
  "abstract_shown": true,
  "affiliations": [
    "Joslin-Beth Israel Deaconess Foot Center and The Rongxiang Xu, MD, Center for Regenerative Therapeutics, Beth Israel Deaconess Medical Center, Harvard Medical S"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 24,
  "authors": [
    {
      "name": "Z. Li"
    },
    {
      "affs": [
        0
      ],
      "name": "G. Theocharidis"
    },
    {
      "name": "S. Lee"
    },
    {
      "name": "N. Kalavros"
    },
    {
      "name": "S. U. Nagalakshmi"
    },
    {
      "name": "M. Contreras"
    },
    {
      "name": "E.-A. Valsami"
    },
    {
      "name": "H. Nam"
    },
    {
      "name": "M. Guan"
    },
    {
      "name": "G. Chu"
    },
    {
      "name": "I. Mezghani"
    },
    {
      "name": "E. Wang"
    },
    {
      "name": "B. J. Sumpio"
    },
    {
      "name": "J. Hou"
    },
    {
      "name": "M. Gennari-Felipe"
    },
    {
      "name": "J. Gilman"
    },
    {
      "name": "N. Lafuente-Gomez"
    },
    {
      "name": "L. Maeso Aragon"
    },
    {
      "name": "N. Dimitrakakis"
    },
    {
      "name": "A. Arruda de Amaral"
    },
    {
      "name": "S. Wang"
    },
    {
      "name": "I. S. Vlachos"
    },
    {
      "name": "D. J. Mooney"
    },
    {
      "name": "A. Veves"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8dadvg53ffsqb.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.11.06.764960",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.11.06.764960v1.full",
  "id": "8dadvg53ffsqb",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.11.06.764960v1",
  "language": null,
  "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": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.11.06.764960v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-06",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/8dadvg53ffsqb.ris",
  "sources": [
    {
      "first_seen": "2026-11-10T00:28:02Z",
      "native_id": "10.64898/2026.11.06.764960",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.11.06.764960v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Cholinergic modulation engages a CHRM1-IL-17 neuroimmune axis to promote diabetic wound repair",
  "title_text": "Cholinergic modulation engages a CHRM1-IL-17 neuroimmune axis to promote diabetic wound repair",
  "type": "preprint",
  "updated_at": "2026-11-10T00:28:02Z",
  "url": "https://research.draconitic.com/paper/8dadvg53ffsqb",
  "venue": "bioRxiv",
  "versions": []
}