{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T16:37:07Z","timestamp":1790095027802,"version":"4.0.1"},"reference-count":219,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000090","name":"Congressionally Directed Medical Research Programs","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000090","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002160","name":"Jain Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002160","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005202","name":"Muscular Dystrophy Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005202","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Inflammation is a tightly regulated process essential for skeletal muscle repair, and its dysregulation contributes to chronic disease and impaired regeneration. Following injury, muscle repair involves a coordinated immune response initiated by neutrophil infiltration, followed by macrophage recruitment and diversification. Rather than existing as discrete subsets, macrophages span a continuum of functional states that evolve over time in response to local environmental cues, enabling transitions from clearing debris and pro-inflammatory signaling to supporting resolution of inflammation, and remodeling and regeneration of the tissue. This functional plasticity is closely linked to intracellular metabolic programs. In this review, we examine how metabolic pathways, particularly the balance between glycolysis and oxidative phosphorylation, govern macrophage behavior through epigenetic mechanisms, thereby coupling cellular metabolism to inflammatory and regenerative gene expression. We further explore how these interconnected pathways are disrupted in chronic inflammatory muscle diseases, including muscular dystrophies. Recent transcriptomic studies highlight pathogenic macrophage populations with altered metabolic and epigenetic profiles that contribute to fibrosis and impaired regeneration. By integrating findings from both acute injury and chronic disease contexts, we provide a framework to explore macrophage function through a metabolic and epigenetic lens and discuss emerging strategies aimed at restoring macrophage plasticity and promoting the resolution of inflammation in muscle disease.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1872583","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T14:53:02Z","timestamp":1787669582000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Macrophage plasticity and metabolic control in muscle repair and disease"],"prefix":"10.3389","volume":"17","author":[{"given":"Sarah","family":"Tiufekchiev-Grieco","sequence":"first","affiliation":[{"name":"Center for Precision Medicine and Genomics Research, Children\u2019s National Research Institute, Children\u2019s National Research and Innovation Campus, Children\u2019s National Hospital","place":["Washington, DC, United States"]},{"name":"Integrated Biomedical Sciences, The George Washington University School of Medicine and Health Sciences","place":["Washington, DC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James S.","family":"Novak","sequence":"additional","affiliation":[{"name":"Center for Precision Medicine and Genomics Research, Children\u2019s National Research Institute, Children\u2019s National Research and Innovation Campus, Children\u2019s National Hospital","place":["Washington, DC, United States"]},{"name":"Department of Pediatrics, The George Washington University School of Medicine and Health Sciences","place":["Washington, DC, United States"]},{"name":"Department of Biochemistry and Molecular Medicine, The George Washington University School of Medicine and Health Sciences","place":["Washington, DC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jyoti 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