{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:00:15Z","timestamp":1790773215355,"version":"4.1.0"},"reference-count":133,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Diabetic foot ulcer healing is compromised because metabolic, inflammatory and tissue-repair processes fail to proceed in a coordinated and timely manner. Persistent hyperglycemia, metabolic stress and oxidative imbalance can reshape immune-cell function and the tissue microenvironment, thereby sustaining inflammatory activation and hindering the transition to a reparative state. However, the epigenetic mechanisms that maintain these maladaptive states and link them to defective tissue regeneration remain incompletely understood. Histone post-translational modifications (hPTMs) constitute a dynamic regulatory layer through which metabolic and inflammatory signals are integrated with chromatin structure and gene expression. Persistent alterations in hPTMs may contribute to molecular imprints associated with metabolic memory, thereby sustaining vascular inflammation and remodeling that may further compromise tissue repair in diabetic foot ulcers. This Review summarizes current evidence for the involvement of histone acetylation, methylation, phosphorylation and metabolism-associated histone modifications in immune dysregulation and impaired diabetic foot ulcer healing. We discuss how hPTM-dependent mechanisms regulate inflammatory activation and resolution, macrophage functional transitions and vascular remodeling, and how these alterations influence angiogenesis, fibroblast-to-myofibroblast differentiation, extracellular matrix remodeling and keratinocyte-mediated re-epithelialization. Particular attention is given to the distinction between evidence derived directly from diabetic foot ulcer studies and evidence extrapolated from other diabetic tissues, non-diabetic wound models and\n                    <jats:italic>in vitro<\/jats:italic>\n                    systems. We also discuss recent direct diabetic wound-model interventions targeting acetylation-related pathways, including the p300\/CBP\u2013ZEB2 axis and restoration of H3K27ac-associated macrophage regulatory states, as well as lactate-oxidizing strategies that modulate lactylation-related responses. These studies provide intervention-based preclinical support for the functional involvement of acetylation and metabolism-associated chromatin regulation in diabetic wound repair, although the responsible histone sites, causal cell populations, treatment windows and relevance to human DFUs remain incompletely defined. Taken together, current evidence supports hPTMs as an important regulatory interface linking the diabetic microenvironment to persistent immune dysregulation, vascular dysfunction and impaired tissue repair. However, the therapeutic relevance of these mechanisms remains difficult to assess because the available evidence is heterogeneous and predominantly preclinical, while the cell specificity, temporal dynamics and clinical applicability of epigenetic interventions remain uncertain.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1957976","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T12:30:16Z","timestamp":1790771416000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Histone post-translational modifications in diabetic foot ulcer healing: linking immune dysregulation to tissue repair"],"prefix":"10.3389","volume":"17","author":[{"given":"JingBo","family":"Hou","sequence":"first","affiliation":[{"name":"Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University","place":["Zunyi, Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JunZhe","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University","place":["Zunyi, Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YueZhong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University","place":["Zunyi, Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ZiYi","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University","place":["Zunyi, Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoxiang","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University","place":["Zunyi, Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengliang","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University","place":["Zunyi, Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shune","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University","place":["Zunyi, Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.4103\/ajm.ajm_53_20","article-title":"Pathophysiology of diabetes: an overview","volume":"10","author":"Banday","year":"2020","journal-title":"Avicenna J 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