{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T05:48:12Z","timestamp":1782712092961,"version":"3.54.5"},"reference-count":100,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system characterized by inflammation, neuroaxonal injury, and progressive neurologic disability. Although its etiology is multifactorial, cigarette smoking is among the most consistent modifiable environmental exposures associated with increased MS risk and worse clinical outcomes. Smoking has been linked to greater inflammatory activity, accelerated disability accumulation, and earlier progression, suggesting effects across multiple stages of disease biology. In this review, we examine the hypothesis that smoking accelerates immune aging, or immunosenescence, and thereby contributes to both early inflammatory disease activity and later neurodegenerative progression. We summarize evidence that smoking promotes immune phenotypes resembling physiologic aging, including contraction of na\u00efve T-cell pools and expansion of terminally differentiated, senescent CD8+ populations. We also discuss potential mechanisms underlying these effects, including oxidative stress, cholinergic signaling, and epigenetic remodeling. By integrating epidemiologic, clinical, and mechanistic evidence, we propose that smoking-associated immune aging acts as a biologic modifier of MS, influencing susceptibility, relapse activity, and long-term progression.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1840928","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T05:41:27Z","timestamp":1782711687000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Smoking accelerates immunosenescence in multiple sclerosis"],"prefix":"10.3389","volume":"17","author":[{"given":"Meerah","family":"Khan","sequence":"first","affiliation":[{"name":"Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation","place":["Oklahoma, OK, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekdanai","family":"Uawithya","sequence":"additional","affiliation":[{"name":"Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation","place":["Oklahoma, OK, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua S.","family":"Mytych","sequence":"additional","affiliation":[{"name":"Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation","place":["Oklahoma, OK, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismail","family":"Muwenda","sequence":"additional","affiliation":[{"name":"Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation","place":["Oklahoma, OK, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Reidy","sequence":"additional","affiliation":[{"name":"Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation","place":["Oklahoma, OK, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert 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