{
  "abstract": "Alcohol-associated liver disease (ALD) is a major cause of liver-related morbidity and mortality, yet no targeted, disease-modifying therapy exists and the immune mechanisms driving disease progression remain poorly defined. Acetylcholine-producing cholinergic immune cells have emerged as regulators of homeostasis across tissues and in disease, but their role in alcohol-induced hepatic stress is unknown. Here, we characterized the hepatic cholinergic immune landscape during alcohol-induced stress using flow cytometry and single-cell RNA-sequencing of ChAT-eGFP reporter mice. Alcohol feeding expanded hepatic cholinergic immune cells, with T cells constituting a substantial and dynamic fraction of this population that showed a broad increase in acetylcholine signaling and shifted towards a repressed, anergy-like transcriptional state. CD4 T cells underwent coordinated suppression of cholesterol biosynthesis, while CD8 T cells instead adopted a cytotoxic activation program. Together, these findings identify cholinergic T cell signaling, and cholesterol metabolism within CD4 T cells specifically, as a previously unrecognized adaptive response to alcohol-induced liver stress, nominating candidate therapeutic targets for a disease that is marred by critically limited treatment options.",
  "abstract_shown": true,
  "affiliations": [
    "University of Michigan"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "name": "A. J. Knights"
    },
    {
      "name": "S. Liu"
    },
    {
      "name": "E. J. Kim"
    },
    {
      "affs": [
        0
      ],
      "name": "J. Wu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/79a86gd9cw60p.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.18.752097",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.18.752097v1.full",
  "id": "79a86gd9cw60p",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.18.752097v1",
  "language": null,
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "immunology"
    ],
    [
      "openalex",
      "2734|Alcohol Consumption and Health Effects"
    ]
  ],
  "openalex": "W7214234444",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.18.752097v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-18",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/79a86gd9cw60p.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:24:23Z",
      "native_id": "10.64898/2026.09.18.752097",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.18.752097v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Hepatic cholinergic T cell signaling mediates an adaptive response to alcohol-induced liver stress",
  "title_text": "Hepatic cholinergic T cell signaling mediates an adaptive response to alcohol-induced liver stress",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:23Z",
  "url": "https://research.draconitic.com/paper/79a86gd9cw60p",
  "venue": "bioRxiv",
  "versions": []
}