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Generally, several types of immune cells play a part, with natural killer (NK) cells being essential. Different subsets of natural killer cells function differently within the course of an autoimmune disease, such as MS. There are mainly two types of natural killers in humans: immature CD56<jats:sup><jats:italic>bright<\/jats:italic><\/jats:sup> CD16<jats:sup>\u2013<\/jats:sup> and mature CD56<jats:sup><jats:italic>dim<\/jats:italic><\/jats:sup> CD16<jats:sup>+<\/jats:sup> natural killers, together with their respective subtypes. Factors from natural killers expand the T cell population and control the process by which native CD4<jats:sup>+<\/jats:sup> T cells differentiate into Th1 or Th2 lymphocytes, which affect autoimmune responses. Natural killer subsets CD56<jats:sup><jats:italic>bright<\/jats:italic><\/jats:sup> and CD56<jats:sup><jats:italic>dim<\/jats:italic><\/jats:sup> may have differing roles in MS development. The impact of these NK cell subsets is influenced by factors such as Granzymes, genetics, infections, TLR, and HSP. We reviewed and evaluated the relationship between natural killer cells and MS.<\/jats:p>","DOI":"10.3389\/fncel.2025.1500770","type":"journal-article","created":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T15:09:41Z","timestamp":1743779381000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Natural killer cells in multiple sclerosis: foe or friends?"],"prefix":"10.3389","volume":"19","author":[{"given":"Fatemeh","family":"Aghaee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammadreza","family":"Abedinpour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saeid","family":"Anvari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alia","family":"Saberi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Fallah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arash","family":"Bakhshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"577353","DOI":"10.1016\/j.jneuroim.2020.577353","article-title":"An immunological and transcriptomics approach on differential modulation of NK cells in multiple sclerosis patients under interferon-\u03b21 and fingolimod therapy.","volume":"347","author":"Acar","year":"2020","journal-title":"J. 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