{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T17:38:16Z","timestamp":1789148296757,"version":"build-2803163510"},"reference-count":95,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CAMS Innovation Fund for Medical Sciences","award":["2021-I2M-1-060"],"award-info":[{"award-number":["2021-I2M-1-060"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: Macrophages were long regarded as passive executors of erythrophagocytosis responsible for systemic iron recycling. However, increasing evidence has reframed them as immunometabolic hubs that sense diverse environmental cues to modulate systemic iron homeostasis. Main body: This review examines the molecular architecture underlying macrophage iron metabolism and outlines how iron metabolic processes are dynamically regulated across spatial and temporal scales through the integration of mechanotransductive, mitochondrial, and epigenetic signaling pathways. Across disease contexts, macrophage iron handling displays marked heterogeneity, exemplified by contact-dependent iron transfer in tumors and ferroptosis-driven instability in cardiovascular disease. In cardiovascular pathologies, iron overload is associated with enhanced ferroptosis-related cascades that contribute to atherosclerotic plaque instability. Furthermore, at mucosal interfaces, host\u2013pathogen competition over nutritional immunity highlights epigenetic strategies by which pathogens perturb host iron machinery. Conclusions: Linking these mechanistic insights to clinical translation, emerging therapeutic strategies are discussed that move beyond non-specific systemic iron chelation toward more targeted interventions. These include engineering macrophages for targeted drug delivery, exploiting nanomedicine-based redox modulation to influence macrophage phenotypes, and non-invasive regulation via the gut microbiota\u2013epigenetic axis. Collectively, elucidating macrophage iron metabolic networks provides a conceptual framework for the development of precision approaches to inflammatory, metabolic, and malignant diseases.<\/jats:p>","DOI":"10.3390\/cells15100895","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T06:42:18Z","timestamp":1779691338000},"page":"895","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Macrophage Iron Metabolism Mediates Immunometabolic Reprogramming and Tissue Homeostasis: From Molecular Mechanisms to Clinical Translation"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-1234-8606","authenticated-orcid":false,"given":"Mingwei","family":"Wang","sequence":"first","affiliation":[{"name":"Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu 610052, China"},{"name":"Key Laboratory of Transfusion Adverse Reactions, Chinese Academy of Medical Sciences, Chengdu 610052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaohui","family":"Ying","sequence":"additional","affiliation":[{"name":"Center of Craniofacial Orthodontics, Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Disease, Shanghai Key Laboratory of Stomatology, Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu 610052, China"},{"name":"Key Laboratory of Transfusion Adverse Reactions, Chinese Academy of Medical Sciences, Chengdu 610052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Lou","sequence":"additional","affiliation":[{"name":"Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu 610052, China"},{"name":"Key Laboratory of Transfusion Adverse Reactions, Chinese Academy of Medical Sciences, Chengdu 610052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuchang","family":"Dai","sequence":"additional","affiliation":[{"name":"Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu 610052, China"},{"name":"Key Laboratory of Transfusion Adverse Reactions, Chinese Academy of Medical Sciences, Chengdu 610052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu 610052, China"},{"name":"Key Laboratory of Transfusion Adverse Reactions, Chinese Academy of Medical Sciences, Chengdu 610052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1152\/physrev.00008.2013","article-title":"Systemic iron homeostasis","volume":"93","author":"Ganz","year":"2013","journal-title":"Physiol. 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