{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T05:20:41Z","timestamp":1793251241159,"version":"4.5.0"},"reference-count":106,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T00:00:00Z","timestamp":1766534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cigarette smoking is the leading preventable cause of chronic diseases (e.g., COPD, cardiovascular disease, cancer), largely driven by persistent immune-inflammatory mechanisms. This review synthesizes the molecular and cellular cascades linking cigarette smoke (CS) exposure to chronic pathology. CS constituents, particularly ROS\/RNS, induce rapid oxidative stress that overwhelms antioxidant defenses and generates damage-associated molecular patterns (DAMPs). These DAMPs activate pattern recognition receptors (PRRs) and the NLRP3 inflammasome, initiating NF-\u03baB signaling and the release of pro-inflammatory cytokines (TNF-\u03b1, IL-1\u03b2, IL-6). CS exposure causes profound innate immune dysregulation, including airway epithelial barrier disruption, hyperactivated neutrophils, and dysfunctional alveolar macrophages (AMs) that release destructive proteases (e.g., MMP-12) and acquire foam-cell\u2013like characteristics. Furthermore, CS drives adaptive immunity toward a Th1\/Th17-dominant phenotype while suppressing regulatory T-cell (Treg) function, thereby promoting autoimmunity and chronic tissue injury. Critically, CS induces epigenetic reprogramming (e.g., DNA methylation, miRNA dysregulation), locking immune cells into a persistent pro-inflammatory state. This convergence of oxidative stress, innate and adaptive immune dysregulation, and epigenetic alterations underlies the systemic low-grade inflammation that fuels smoking-related chronic diseases, highlighting key targets for novel therapeutic interventions.<\/jats:p>","DOI":"10.3390\/ijms27010187","type":"journal-article","created":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T09:58:34Z","timestamp":1766570314000},"page":"187","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["The Convergent Immunopathogenesis of Cigarette Smoke Exposure: From Oxidative Stress to Epigenetic Reprogramming in Chronic Disease"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2965-6102","authenticated-orcid":false,"given":"Aysen Kutan","family":"Fenercioglu","sequence":"first","affiliation":[{"name":"Department of Family Medicine, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul 34098, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1347-8498","authenticated-orcid":false,"given":"Hafize","family":"Uzun","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Medicine, Istanbul Atlas University, Istanbul 34403, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0754-1240","authenticated-orcid":false,"given":"Durisehvar Ozer","family":"Unal","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Faculty of Pharmacy, Istanbul University, Istanbul 34116, T\u00fcrkiye"},{"name":"Drug Research and Application Center, Istanbul University, Istanbul 34116, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,24]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2021). 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