{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:31:17Z","timestamp":1792794677458,"version":"4.5.0"},"reference-count":125,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":148,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"General Secretariat for Research and Innovation of Greece"},{"name":"National Recovery and Resilience Plan Greece 2.0"},{"name":"European Union-Next Generation EU","id":[{"id":"https:\/\/ror.org\/019w4f821","id-type":"ROR","asserted-by":"crossref"}]},{"name":"General Secretariat for Research and Innovation of Greece","award":["2024\u039d\u039111900001"],"award-info":[{"award-number":["2024\u039d\u039111900001"]}]},{"name":"National Recovery and Resilience Plan Greece 2.0"},{"name":"National Program for Development"},{"DOI":"10.13039\/501100013209","name":"Hellenic Foundation for Research and Innovation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013209","id-type":"DOI","asserted-by":"publisher"}]},{"name":"3rd Call for Hellenic Foundation for Research and Innovation","award":["6671"],"award-info":[{"award-number":["6671"]}],"id":[{"id":"https:\/\/ror.org\/05v75r592","id-type":"ROR","asserted-by":"crossref"}]},{"name":"The King Salman Center for Disability Research","award":["KSRG-2023-305"],"award-info":[{"award-number":["KSRG-2023-305"]}],"id":[{"id":"https:\/\/ror.org\/01ht2b307","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Fulbright Foundation U.S. Student Grant Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Macrophages, the central mediators of innate immune responses, can adapt and build nonspecific memory, also known as innate immune memory or trained immunity. Training of macrophages occurs through epigenetic changes and metabolic rewiring, which fuels macrophage responsiveness. In addition to training in response to infectious insults, macrophage responsiveness can be modulated by pathogenic de-regulation of hormones, cytokines, or adipokines, which similarly induce epigenetic changes in inflammatory genes. Sex specific differences in macrophage responsiveness to TLR ligands have been described, with sex hormones playing a crucial role in shaping the epigenetic landscape and regulating inflammatory responses. Chronic metabolic disorders, such as obesity and type 2 diabetes, also affect macrophage responsiveness. In particular, insulin resistance impairs Akt signaling in macrophages in an Akt isoform-specific manner, altering their metabolism, their responsiveness to inflammatory insults and their capacity to eliminate pathogens. These functional impairments are underpinned by changes in the epigenetic landscape of macrophages. Given the short half-life of macrophages in the periphery, these long-lasting alterations in their responsiveness originate in the bone marrow at the level of hematopoietic stem and progenitor cells. Recent studies have demonstrated that exposure to TLR ligands induces immunological memory driven by changes in hematopoietic stem and progenitor cells. These changes include epigenetic alterations in histones and DNA. Herein we discuss recent evidence on the epigenetic and metabolic regulation of macrophage memory, highlight sex hormone-driven changes, describe changes driven by metabolic factors and obesity, and explore the therapeutic potential of targeting epigenetic regulators for the treatment of inflammatory diseases.<\/jats:p>","DOI":"10.1093\/jimmun\/vkaf135","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T15:20:33Z","timestamp":1751383233000},"page":"2812-2821","source":"Crossref","is-referenced-by-count":38,"title":["Epigenetic and metabolic regulation of macrophage responsiveness and memory"],"prefix":"10.1093","volume":"214","author":[{"given":"Maria G","family":"Daskalaki","sequence":"first","affiliation":[{"name":"Laboratory of Clinical Chemistry, School of Medicine, University of Crete , Heraklion,","place":["Greece"]},{"name":"Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology Hellas , Heraklion,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioanna","family":"Lapi","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology Hellas , Heraklion,","place":["Greece"]},{"name":"Department of Pediatrics, School of Medicine, University of Crete , Heraklion,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avery Ellen","family":"Hurst","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Chemistry, School of Medicine, University of Crete , Heraklion,","place":["Greece"]},{"name":"Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology Hellas , Heraklion,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Al-Qahtani","sequence":"additional","affiliation":[{"name":"Department of Infection and Immunity, Research Center, King Faisal Specialist Hospital and Research Center , Riyadh,","place":["Saudi Arabia"]},{"name":"Department of Microbiology and Immunology, College of Medicine, Alfaisal University , Riyadh,","place":["Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Vergadi","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology Hellas , Heraklion,","place":["Greece"]},{"name":"Department of Pediatrics, School of Medicine, University of Crete , Heraklion,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1214-4151","authenticated-orcid":false,"given":"Christos","family":"Tsatsanis","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Chemistry, School of Medicine, University of Crete , Heraklion,","place":["Greece"]},{"name":"Institute of Molecular Biology and Biotechnology, Foundation for Research and 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