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In this review, we compile evidence suggesting that trained immunity\u2014a form of innate immune memory\u2014may play a crucial role in the autoimmune component of MS. By examining key findings from immunology, neuroinflammation, and MS pathophysiology, we explore how innate immune cells, particularly monocytes and macrophages, could contribute to disease onset and progression through persistent pro-inflammatory responses. Understanding the impact of trained immunity in MS could open new avenues for therapeutic strategies targeting the innate immune system.<\/jats:p>","DOI":"10.3390\/cells14141054","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T09:38:27Z","timestamp":1752140307000},"page":"1054","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Cues of Trained Immunity in Multiple Sclerosis Macrophages"],"prefix":"10.3390","volume":"14","author":[{"given":"Elisa","family":"Popa","sequence":"first","affiliation":[{"name":"Institut du Cerveau\u2014Paris Brain Institute\u2014ICM, Inserm, CNRS, APHP, H\u00f4pital Piti\u00e9 Salp\u00eatri\u00e8re University Hospital, Sorbonne Universit\u00e9, DMU Neuroscience 6, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9l\u00e8ne","family":"Cheval","sequence":"additional","affiliation":[{"name":"Institut du Cerveau\u2014Paris Brain Institute\u2014ICM, Inserm, CNRS, APHP, H\u00f4pital Piti\u00e9 Salp\u00eatri\u00e8re University Hospital, Sorbonne Universit\u00e9, DMU Neuroscience 6, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2741-6052","authenticated-orcid":false,"given":"Violetta","family":"Zujovic","sequence":"additional","affiliation":[{"name":"Institut du Cerveau\u2014Paris Brain Institute\u2014ICM, Inserm, CNRS, APHP, H\u00f4pital Piti\u00e9 Salp\u00eatri\u00e8re University Hospital, Sorbonne Universit\u00e9, DMU Neuroscience 6, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.chom.2011.04.006","article-title":"Trained immunity: A memory for innate host defense","volume":"9","author":"Netea","year":"2011","journal-title":"Cell Host Microbe"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1186\/s12967-023-03944-8","article-title":"BCG-induced trained immunity: History, mechanisms and potential applications","volume":"21","author":"Chen","year":"2023","journal-title":"J. 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