{
  "abstract": "Inflammatory signals are broadly conserved, yet how tissue context converts them into programs of recovery or maladaptive repair remains unclear. Using kidney injury as a model of inflammation-to-repair transitions, we identify an injury-induced proximal-tubule complement program in which cell-intrinsic complement proteins are repurposed across subcellular compartments to couple inflammation to metabolic and chromatin regulation and promote maladaptive fibrotic remodeling. Mechanistically, myeloid-derived IL-1b; signals through IL-1R1 on injured tubular cells to recruit NF-kB and AP-1 to C3 and Cfb, coordinately inducing complement component 3 (C3) and Factor B (FB). Cytoplasmic FB drives cleavage-activation of cell-intrinsic C3, which supports tubular cell mitochondrial metabolic adaptation to stress and accumulation of C3aR-expressing macrophages around injured tubules. Nuclear FB, on the other hand, binds chromatin through a previously unrecognized DNA-binding interface and mediates histone H3 proteolysis and the preferential remodeling of chromatin promotors enriched in transcriptional programs relevant to maladaptive repair. Key features of this injury-associated C3-FB response, including intranuclear FB, are conserved in human kidney disease, associate with kidney dysfunction, and distinguish diseased from healthy kidneys. Together, these findings suggest that extracellular complement-targeting therapies may miss disease-relevant intracellular functions and suggest nuclear FB as a distinct target whose chromatin interaction and processing capacity could selectively limit maladaptive tissue responses beyond conventional inhibition.",
  "abstract_shown": true,
  "affiliations": [
    "National Institutes of Health"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 25,
  "authors": [
    {
      "name": "T. Freiwald"
    },
    {
      "name": "D. Chauss"
    },
    {
      "name": "M. Tajmul"
    },
    {
      "name": "J. L. Trujillo-Ochoa"
    },
    {
      "name": "D. Kumar"
    },
    {
      "name": "J. Ma"
    },
    {
      "name": "M. Snyder"
    },
    {
      "name": "N. Cheru"
    },
    {
      "name": "J. F. Jaeger"
    },
    {
      "name": "Y. Zhuang"
    },
    {
      "name": "J. B. Gregor"
    },
    {
      "name": "G. Ganne"
    },
    {
      "name": "L. Wang"
    },
    {
      "name": "Y. Guo"
    },
    {
      "name": "M. Gunkel"
    },
    {
      "name": "T. Huber"
    },
    {
      "name": "T. Wiech"
    },
    {
      "name": "E. E. West"
    },
    {
      "name": "S. Ayyadevara"
    },
    {
      "name": "M. Kolev"
    },
    {
      "name": "S. Briggs"
    },
    {
      "name": "C. Kemper"
    },
    {
      "name": "M. Kazemian"
    },
    {
      "name": "D. Portilla"
    },
    {
      "affs": [
        0
      ],
      "name": "B. Afzali"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9v8j5nyath3m4.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.04.756581",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.04.756581v1.full",
  "id": "9v8j5nyath3m4",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.04.756581v1",
  "language": null,
  "licence": "CC0-1.0",
  "licence_label": "CC0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/publicdomain/zero/1.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "immunology"
    ],
    [
      "openalex",
      "2403|Complement system in diseases"
    ]
  ],
  "openalex": "W7221450628",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.04.756581v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-04",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/9v8j5nyath3m4.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:27:11Z",
      "native_id": "10.64898/2026.10.04.756581",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.04.756581v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Intracellular complement Factor B couples inflammatory sensing to metabolism, chromatin regulation and maladaptive tissue repair",
  "title_text": "Intracellular complement Factor B couples inflammatory sensing to metabolism, chromatin regulation and maladaptive tissue repair",
  "type": "preprint",
  "updated_at": "2026-10-30T12:27:11Z",
  "url": "https://research.draconitic.com/paper/9v8j5nyath3m4",
  "venue": "bioRxiv",
  "versions": []
}