{
  "id": 4652957,
  "title": "Cell-intrinsic complement C3 suppresses IFN-β production in macrophages",
  "url": "https://urgent.news/2026/08/31/cell-intrinsic-complement-c3-suppresses-ifn-production-in-macrophages",
  "topic": "science",
  "section": "Science",
  "published": "2026-08-31T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.08.26.746684v1?rss=1"
  },
  "original_language": "en",
  "account": "The cell-intrinsic complement system plays a crucial role in regulating cell-physiological processes, with complement components interacting with intracellular effector systems to modulate responses to pathogens or harmful stimuli. In a recent study, researchers explored whether cell-intrinsic C3 influences inflammatory responses in macrophages. Upon examining LPS-stimulated C3 knockout THP-1-derived macrophages, they found that IFN-β production was significantly heightened, alongside a rise in interferon-stimulated gene expression and increased secretion of IFN-induced cytokines and chemokines. Upon further analysis, C3-deficient cells exhibited elevated phosphorylation of IRF3 at Ser396 and a more stable interaction between IRF3 and TBK1. This resulted in enhanced IRF3 dimerization and nuclear translocation. Notably, TBK1 phosphorylation remained unchanged, suggesting that C3 primarily restricts IRF3-TBK1 complex formation rather than the initial TBK1 activation. The researchers also discovered that small-molecule inhibitors of complement factors B and D could restore full-length C3 abundance in LPS-stimulated primary human macrophages, leading to a decrease in LPS-induced IFN-β production. These findings demonstrate that full-length, uncropped C3 suppresses IFN-β production in human macrophages, emphasizing the significance of the cell-intrinsic complement system in fine-tuning inflammatory responses to pathogens.",
  "summary": "The cell-intrinsic complement system has emerged as an important orchestrator of a variety of cell-physiological processes, with complement components interacting with intracellular effector systems to regulate cellular responses to pathogens or noxious stimuli. For instance, intracellular C5 signaling through a mitochondrial C5a receptor (C5aR1) controls IL-1{beta} production in human monocytes…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}