{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:28:46Z","timestamp":1791491326579,"version":"4.3.4"},"reference-count":172,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"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>Inflammatory bowel disease (IBD) comprises a group of chronic and relapsing intestinal inflammatory disorders whose pathogenesis and progression are closely associated with disruption of the intestinal mucosal barrier, dysregulated immune responses, and altered epigenetic regulation. The innate immune system is a central component of mucosal host defense and plays a pivotal role in pathogen recognition, inflammatory signal transduction, immune-cell functional regulation, and maintenance of barrier homeostasis. In recent years, DNA methylation has been increasingly recognized as an important mechanism contributing to the development and persistence of innate immune dysregulation in IBD by modulating the transcriptional activity of immune-related genes, inflammatory pathway genes, and barrier-function genes. Conversely, persistently activated innate immune responses may reshape DNA methylation patterns through inflammatory cytokines, oxidative stress, and signaling pathways such as NF-\u03baB and JAK\/STAT, thereby forming a dynamic bidirectional regulatory network. This review systematically summarizes the mechanisms underlying the crosstalk between DNA methylation and the innate immune system in IBD, with particular emphasis on its potential roles in inflammatory initiation, immune-cell infiltration, stabilization of pro-inflammatory phenotypes, mucosal barrier injury, inflammatory memory, and disease relapse. We further propose a conceptual framework termed the \u201cDNA methylation\u2013innate immunity interaction axis.\u201d Current evidence suggests that this interaction axis may provide a new mechanistic perspective for understanding the maintenance of chronic inflammation and recurrent disease activity in IBD. It may also offer a theoretical basis for combined epigenetic\u2013immune interventions, biomarker development, and optimization of precision therapeutic strategies. Future studies integrating single-cell omics, spatial omics, longitudinal cohorts, and functional validation are warranted to further define the cell-type specificity, stage-dependent effects, and clinical translational potential of this axis.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1877804","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T05:43:29Z","timestamp":1780983809000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Mechanisms and therapeutic prospects of DNA methylation\u2013mucosal innate immunity crosstalk in inflammatory bowel disease"],"prefix":"10.3389","volume":"17","author":[{"given":"Tao","family":"Zhang","sequence":"first","affiliation":[{"name":"Liaoning University of Traditional Chinese Medicine","place":["Shenyang, China"]},{"name":"Second Affiliated Hospital, Liaoning University of Traditional Chinese Medicine","place":["Shenyang, 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China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Wei","sequence":"additional","affiliation":[{"name":"Liaoning University of Traditional Chinese Medicine","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Wang","sequence":"additional","affiliation":[{"name":"Liaoning University of Traditional Chinese Medicine","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ru","family":"Man","sequence":"additional","affiliation":[{"name":"Liaoning University of Traditional Chinese Medicine","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jirun","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Beijing Shijitan Hospital, Capital Medical University","place":["Beijing, China"]},{"name":"Ninth School of Clinical Medicine, Peking University","place":["Beijing, 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