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Following injury, macrophages transition from proinflammatory to anti-inflammatory phenotypes, regulating debris clearance, cytokine secretion, and the activity of fibro-adipogenic progenitors and muscle stem cells. Fibro-adipogenic progenitors transiently support muscle stem cell-mediated regeneration but, if not cleared appropriately, differentiate into fibroblasts or adipocytes, contributing to fibrosis and fatty infiltration. Dysregulated macrophage\u2013fibro-adipogenic progenitor crosstalk drives pathological conditions, including Duchenne muscular dystrophy and age-related sarcopenia, where imbalances in cytokines and growth factors exacerbate maladaptive remodeling. Fibro-adipogenic progenitor-derived colony-stimulating factor 1 sustains macrophage survival while macrophage-derived signals, including tumor necrosis factor alpha and transforming growth factor beta, regulate fibro-adipogenic progenitor apoptosis, proliferation, and differentiation, shaping the regenerative niche. Single-cell and spatial transcriptomic approaches have revealed extensive heterogeneity among resident and infiltrating macrophages and fibro-adipogenic progenitor subsets, uncovering the molecular circuits underlying intercellular communication. Therapeutic strategies targeting cytokines and growth factors show promise in restoring balanced macrophage\u2013fibro-adipogenic progenitor signaling, enhancing regeneration, and limiting fibrosis and fatty infiltration. Understanding the temporal dynamics of macrophage\u2013fibro-adipogenic progenitor interactions is essential for developing interventions that preserve muscle homeostasis and counteract degenerative disease.<\/jats:p>","DOI":"10.1093\/jleuko\/qiag054","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T11:29:37Z","timestamp":1777289377000},"source":"Crossref","is-referenced-by-count":1,"title":["Macrophage and fibro-adipogenic progenitor communication in skeletal muscle regeneration: tissue homeostasis and pathogenic remodeling"],"prefix":"10.1093","volume":"118","author":[{"given":"Seily","family":"Shrestha","sequence":"first","affiliation":[{"name":"Department of Biomedical and Molecular Sciences, Queen's University , 18 Stuart Street, Kingston, Ontario K7L 3N6 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abbey L","family":"Politeski","sequence":"additional","affiliation":[{"name":"Department of Medicine, Queen's University , 18 Stuart Street, Kingston, Ontario K7L 3N6 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0683-2900","authenticated-orcid":false,"given":"Sarah A","family":"Dick","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences, Queen's University , 18 Stuart Street, Kingston, Ontario K7L 3N6 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,4,28]]},"reference":[{"key":"2026051723463174600_qiag054-B1","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1007\/s00223-014-9915-y","article-title":"Skeletal muscle: a brief review of structure and function","volume":"96","author":"Frontera","year":"2015","journal-title":"Calcif Tissue 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