{
  "abstract": "Lactate is a metabolic substrate, an extracellular signaling molecule, and a precursor for protein lactylation, with diverse effects on macrophage immunity. Evidence from infection, tissue injury, efferocytosis, and cancer indicates that lactate-associated pathways can amplify inflammation, support resolution and tissue repair, or sustain immune suppression. These outcomes depend on the timing, cellular source and compartment, chemical formulation and pH, transport and receptor engagement, and the chemistry and targets of lactylation. In this narrative review, we critically synthesize the biochemical foundations of lactate metabolism and lactyl-group donation and examine the mechanisms underlying these distinct macrophage responses. We distinguish model-specific biphasic responses from a universal sequence of early inflammation followed by resolution, and separate reparative programs from impaired antimicrobial or antitumor immunity. We also evaluate evidence for histone and non-histone lactylation, emphasizing the limits of metabolic perturbations and chromatin associations for establishing site-specific causality. This framework identifies experimental variables that should be controlled and supports context-selective investigation of lactate-related therapeutic targets in inflammatory diseases and cancer.",
  "abstract_shown": true,
  "affiliations": [
    "School of Medicine, Northwest University, Xi’an 710069, China",
    "Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China",
    "Department of Burns, Plastic and Wound Repair Surgery, the Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an 710004, China",
    "Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi’an 710032, China"
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Qingshuang Guo"
    },
    {
      "affs": [
        2
      ],
      "name": "Pan Ren"
    },
    {
      "affs": [
        1
      ],
      "name": "Lanqi He"
    },
    {
      "affs": [
        1
      ],
      "name": "Jiaying Gao"
    },
    {
      "affs": [
        0
      ],
      "name": "Ruiqi Lu"
    },
    {
      "affs": [
        3
      ],
      "name": "Yitian Wang"
    },
    {
      "affs": [
        3
      ],
      "name": "Zhiheng Zhang",
      "orcid": "0009-0006-3514-2502"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaohui Han"
    },
    {
      "affs": [
        1
      ],
      "name": "Xi Zhang"
    },
    {
      "affs": [
        3
      ],
      "name": "Chao Fang",
      "orcid": "0000-0003-1011-2113"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7h2ec04svrwqx.bib",
  "cited_by": 0,
  "doi": "10.3390/metabo16100788",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13706687/?tool=EBI",
  "id": "7h2ec04svrwqx",
  "issns": [
    "2218-1989"
  ],
  "landing_url": "https://www.mdpi.com/2218-1989/16/10/788",
  "language": "eng",
  "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",
      "2403|Immune cells in cancer"
    ]
  ],
  "openalex": "W7222700426",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13706687/pdf/?tool=EBI",
  "pmcid": "PMC13706687",
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/7h2ec04svrwqx.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:00Z",
      "native_id": "10.3390/metabo16100788",
      "source": "crossref",
      "url": "https://www.mdpi.com/2218-1989/16/10/788"
    },
    {
      "first_seen": "2026-10-30T12:21:45Z",
      "native_id": "PMC:PMC13706687",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13706687"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Immune cells in cancer",
      "subfield": "immunology"
    }
  ],
  "title": "Lactate-Driven Biphasic Reprogramming of Macrophage Immune Responses",
  "title_text": "Lactate-Driven Biphasic Reprogramming of Macrophage Immune Responses",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:45Z",
  "url": "https://research.draconitic.com/paper/7h2ec04svrwqx",
  "venue": "Metabolites",
  "versions": []
}