{
  "abstract": "Idiopathic pulmonary fibrosis (IPF) is characterized by recurrent alveolar epithelial injury, maladaptive repair, fibroblast activation, and extracellular-matrix accumulation. Lactate metabolism is increasingly implicated in communication between stromal and immune cells in fibrotic lung niches through monocarboxylate transporter (MCT)-mediated transport, hydroxycarboxylic acid receptor 1 (HCAR1/GPR81) sensing, extracellular acidification, and lysine lactylation. This narrative review evaluates the evidence for directional lactate-associated fibroblast–macrophage signaling, the limits of proposed reciprocal interactions, and their therapeutic implications. Human IPF observations, experimental pulmonary-fibrosis studies, and indirect evidence from other disease contexts are separated according to disease relevance and causal resolution. The strongest direct mechanistic evidence supports lactate released by activated myofibroblasts as a stimulus for macrophage histone lactylation and profibrotic transcription, whereas reciprocal macrophage-to-fibroblast lactate feedback remains unproven. Among the lactate-associated targets reviewed, fibroblast-associated MCT4 currently has the most developed preclinical evidence package, supported by disease-relevant observations, target perturbation, and antifibrotic activity in experimental models. However, no lactate-directed therapeutic strategy has yet demonstrated clinical efficacy in IPF. HCAR1/GPR81, lactate-production pathways, and lactylation-associated machinery remain mechanistically compelling but are at earlier stages of pharmacological validation. Overall, available evidence is more consistent with lactate functioning as a context-dependent amplifier or maintenance signal than with a demonstrated uniform initiating role in IPF. Lactate-directed interventions may therefore be considered adjunctive strategies alongside established antifibrotic therapy. Further translation will require cell- and disease-stage-specific causal validation, lesion-resolved target engagement, efficacy in established fibrosis, and a therapeutic window that preserves physiological lactate metabolism.",
  "abstract_shown": true,
  "affiliations": [
    "School of Integrated Traditional Chinese and Western Medicine, Tianjin University of Traditional Chinese Medicine",
    "Department of Infectious Diseases, Characteristic Medical Center of Chinese People’s Armed Police Force",
    "School of Medical Technology, Tianjin University of Traditional Chinese Medicine"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yuntao Wu"
    },
    {
      "affs": [
        0
      ],
      "name": "Xinli Song"
    },
    {
      "affs": [
        1
      ],
      "name": "Bin Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuehua Han"
    },
    {
      "affs": [
        2
      ],
      "name": "Chen Zheng"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaoxu Zhao"
    },
    {
      "affs": [
        2
      ],
      "name": "Tianyu Zhu"
    },
    {
      "affs": [
        0
      ],
      "name": "Meng Yuan"
    },
    {
      "affs": [
        0
      ],
      "name": "Huihui Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Yue Wang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4v6ef68vancg7.bib",
  "cited_by": 0,
  "doi": "10.3389/fphar.2026.1989965",
  "fulltext_url": null,
  "id": "4v6ef68vancg7",
  "issns": [
    "1663-9812"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1989965/full",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2740|Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis"
    ]
  ],
  "openalex": "W7223706289",
  "pdf_url": "https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2026.1989965/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-26",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/4v6ef68vancg7.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:06Z",
      "native_id": "10.3389/fphar.2026.1989965",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1989965/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "issn:1663-9812",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Lactate-associated fibroblast–macrophage signaling in idiopathic pulmonary fibrosis: evidence boundaries and immunopharmacological opportunities",
  "title_text": "Lactate-associated fibroblast–macrophage signaling in idiopathic pulmonary fibrosis: evidence boundaries and immunopharmacological opportunities",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:06Z",
  "url": "https://research.draconitic.com/paper/4v6ef68vancg7",
  "venue": "Frontiers in Pharmacology",
  "versions": []
}